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Biomedical subjects

M Roberts

Publications and source records attributed to M Roberts.

At least 19 recordsLinked to original sources

Stomatal behavior of ozone-sensitive and -insensitive coneflowers (Rudbeckia laciniata var. digitata) in Great Smoky Mountains National Park.

* Morphological and physiological attributes were assessed to elucidate the underlying mechanisms of ozone (O(3)) sensitivity in a highly sensitive species, cutleaf coneflower (Rudbeckia laciniata var. digitata). * Foliage at the same height in the canopy on paired O(3)-sensitive and -insensitive cutleaf coneflowers was assessed for level of foliar symptoms, stomatal density, stomatal responsiveness to dynamic changes in light and leaf-to-air vapor pressure deficit (VPD), steady-state responses to light and CO(2), intrinsic transpirational efficiency, and plant water balance. * There were no morphological differences between the sensitivity types that might have contributed to greater O(3) uptake in sensitive individuals. Stomata of sensitive plants were less responsive than those of insensitive plants to experimentally increased and decreased light intensities, and to increased VPD. O(3)-insensitive plants had greater intrinsic transpirational efficiencies, greater maximum assimilation rates under saturating CO(2) and light, and greater carboxylation rates. * Different physiological attributes vary independently within an individual plant, which collectively confer sensitivity or insensitivity to O(3) injury.

Carbon Dioxide↗

Colposcopic management of high-grade referral smears: a retrospective audit supporting 'see and treat'?

OBJECTIVE: The National Health Service Cervical Screening Programme monitors the quality of colposcopy services through the annual KC65 returns. The 2002 returns demonstrated that Standard 7c, which specifies a biopsy rate > or = 90% at first colposcopy visit for high-grade referrals, was not met in the assessed 3-month period. This was investigated along with the other standards. METHODS: Retrospective colposcopy records were accessed for the 597 new referrals, excluding 10 pregnant patients, seen at the colposcopy clinic at the Royal Victoria Infirmary between 1 July 2001 and 31 December 2002, following an abnormal high-grade smear. Cytology and histopathology computer records were checked for confirmation. The results were assessed against the colposcopy standards applicable at that time and the revised standards (2004). RESULTS: Biopsies were taken from 94.47% (Standard > or = 90%) of women at index colposcopy visit including wire loop excision biopsies from 66.16% (87.97% of high-grade colposcopic appearances). Cervical intraepithelial neoplasia (CIN) on histology was found in 91.79% in the study group (Standard > or = 85%) and in 96.71% of index visit biopsies (Standard > or = 90%), meeting the applicable colposcopy standards. The revised 2004 standards specify a biopsy in > or = 95% of high-grade referrals and excision biopsies in 95% if colposcopic appearances are also high-grade, if colposcopy is low grade but the smear is severely dyskaryotic, or when the lesion extends into the canal. The positive predictive value of high-grade cytology for this entire group was 75.54% with CIN present in 90.95%. CONCLUSION: From this study it appears that high-grade cytology in this centre reliably indicates high-grade CIN. Therefore, in women referred for colposcopy following a high-grade smear, excision biopsies should be performed in a higher proportion at the first visit to comply with the revised standards.

Biopsy↗

Public investment in strengthening Veterinary Services and other food safety authorities: issues affecting developed and developing countries.

During the negotiation of the Agreement on the Application of Sanitary and Phytosanitary Measures (the SPS Agreement), there was clear recognition of the problems that developing countries would face in complying with the SPS Agreement. The agreement included provisions related to technical assistance and special differential treatment for developing countries. Both topics are discussed in the SPS Committee as a regular agenda item and have been subject to substantive consideration during both reviews of the SPS Agreement, in 1999 and latterly in 2005. The SPS Committee is currently considering proposals to make these provisions more precise, effective and operational. The Standards and Trade Development Facility (STDF) was formally established in mid-2002 by the Food and Agriculture Organization, World Organisation for Animal Health (OIE), World Bank, World Health Organization and World Trade Organization as a financing and coordinating mechanism. The STDF maintains a database which provides information on SPS-related technical assistance and capacity-building projects. From the limited data gathered, it would appear that the focus of the technical assistance provided so far has been knowledge transfer. Only a small minority of the projects reported deal with the strengthening of hard infrastructure such as laboratory facilities. It is also clear that in terms of the overall number and value of projects, animal health lags well behind the food safety sector. The World Bank estimates that annual expenditure by donor agencies on trade-related SPS programmes has been running at some USdollars 65 million to USdollars 70 million annually. However, there is under-reporting of technical cooperation activities in the STDF database.

Animals↗

The development of a high-density canine microarray.

DNA microarrays can give global transcriptional views of cellular responses to disease, development, nutrition, and other biological states. They can be used to elucidate biological networks, develop diagnostics, and identify genetic targets and molecular mechanisms. The technology is widely used and can be a valuable complement to more "disease-centric" focused arrays. For these reasons, Nestlé designed a custom canine Affymetrix microarray representing transcripts from multiple tissues for use in areas where a more focused microarray had not already been developed. Sufficient numbers of sequences representing messenger RNAs (mRNAs) or expressed sequence tags (ESTs) is integral for the design of a global microarray chip. This chip was designed using public domain sequences (GenBank) and sequences from a proprietary canine EST database. In order to enrich the chip with annotated transcripts, both of these sequence sets were BLASTed against the nonredundant protein database. The sequences on the microarray were isolated from more than 48 different tissues. The final compliment of sequences had sequences unique to GenBank (3160), unique to the proprietary EST database (17,620), and present in both sources (1996). In comparison with human sequences (RefSeq), 74% of the canine sequences matched a human sequence.

Animals↗

Inter- and intralaboratory variation of in vitro diffusion cell measurements: an international multicenter study using quasi-standardized methods and materials.

In vitro measurements of skin absorption are an increasingly important aspect of regulatory studies, product support claims, and formulation screening. However, such measurements are significantly affected by skin variability. The purpose of this study was to determine inter- and intralaboratory variation in diffusion cell measurements caused by factors other than skin. This was attained through the use of an artificial (silicone rubber) rate-limiting membrane and the provision of materials including a standard penetrant, methyl paraben (MP), and a minimally prescriptive protocol to each of the 18 participating laboratories. "Standardized" calculations of MP flux were determined from the data submitted by each laboratory by applying a predefined mathematical model. This was deemed necessary to eliminate any interlaboratory variation caused by different methods of flux calculations. Average fluxes of MP calculated and reported by each laboratory (60 +/- 27 microg cm(-2) h(-1), n = 25, range 27-101) were in agreement with the standardized calculations of MP flux (60 +/- 21 microg cm(-2) h(-1), range 19-120). The coefficient of variation between laboratories was approximately 35% and was manifest as a fourfold difference between the lowest and highest average flux values and a sixfold difference between the lowest and highest individual flux values. Intralaboratory variation was lower, averaging 10% for five individuals using the same equipment within a single laboratory. Further studies should be performed to clarify the exact components responsible for nonskin-related variability in diffusion cell measurements. It is clear that further developments of in vitro methodologies for measuring skin absorption are required.

Clinical Laboratory Techniques↗

Acrylamide reduction in processed foods.

The discovery of the formation of acrylamide in fried and baked foods containing high levels of starch and the amino acid asparagine, prompted widespread concern. Both processed and home cooked foods are affected and this has led to the increased study of variations in cooking and processing conditions to minimize formation. While changes in cooking protocols have been in part successful, particularly when lower frying and baking temperatures are used, pretreatments to reduce levels of acrylamide by prevention of formation or acceleration of destruction have been investigated. In this study, a range of pretreatments of grilled potato were investigated and compared with surface washing to remove asparagine and reducing sugars. Synergies were observed between different treatments, and reductions of up to 40% were achieved in a non-optimized system.

Acrylamide↗

Measurement of the flux of ultrahigh energy cosmic rays from monocular observations by the High Resolution Fly's Eye experiment.

We have measured the cosmic ray spectrum above 10(17.2) eV using the two air-fluorescence detectors of the High Resolution Fly's Eye observatory operating in monocular mode. We describe the detector, phototube, and atmospheric calibrations, as well as the analysis techniques for the two detectors. We fit the spectrum to a model consisting of galactic and extragalactic sources.

Journal Article↗

Cerebral vasculitis caused by Aspergillus species in an immunocompetent adult.

We describe a case of cerebral vasculitis due to Aspergillus infection in an immunocompetent adult, in whom the probable source was paranasal sinus infection. At postmortem there was widespread endovascular Aspergillus infection of the cerebral arteries with occlusion of the basilar artery. We review the literature regarding intracranial Aspergillus infection and new approaches to diagnosis.

Aged↗

Psychiatric ethics; a critical introduction for mental health nurses.

Drawing upon the author's experience as a mental health nurse lecturer, this paper suggests that many mental health nurses seem to have difficulty engaging with the ethical issues in psychiatry, and appreciating the relevance of those issues to their everyday practice. In an attempt to address this difficulty, this paper will present a framework that can serve as an accessible introduction to the ethical issues in psychiatry. Reflecting upon general, clinical examples from psychiatric practice, it will be suggested that many ethical issues in psychiatry are concerned with acts of paternalism and with the common justification for those acts. Having presented this framework, the paper will then subject it to a preliminary critique by drawing upon contemporary, critical approaches to health care ethics. It is hoped that this will serve to stimulate both a deeper appreciation of the relevance of ethics to the practice of mental health nursing and an ongoing critical consideration of the ethical issues in psychiatry.

Ethics, Nursing↗

Safety of DNA and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers.

A series of phase I clinical studies were conducted to evaluate the safety of plasmid DNA and modified vaccinia virus Ankara malaria vaccines. The vaccines each encoded a polyepitope string fused to whole Plasmodium falciparum TRAP antigen. Forty-three healthy adult volunteers received the vaccines alone or in DNA/MVA prime-boost combinations. The DNA vaccine was administered either intramuscularly by needle or intradermally by a needleless delivery device. The MVA vaccine was administered intradermally by needle. The vaccines were well-tolerated by all three routes and in various DNA/MVA immunisation regimes. There were no severe or serious adverse events.

Adult↗

Subtyping borderline nuclear changes: is it of value in predicting high-grade cervical intraepithelial neoplasia on histology?

The aim was to determine the association between the subtypes of borderline nuclear changes (BNC) in cervical smears and high-grade cervical intraepithelial neoplasia (HCIN). BNC was reported in 23236 smears received in our laboratory over a 7-year period, 3278 patients were referred for colposcopy. Analysis was restricted to 2007 cases, which fitted the criteria of: (1). consistent subtyping of borderline change and (2). cervical histology result within 12 months of the last abnormal smear. BNC was reported in six categories and correlated with histology. Atypia bordering on dyskaryosis, atypical metaplastic cells and endocervical atypia, were associated with HCIN in 25%, 25.4% and 23.8% of cases, respectively. Dyskeratosis and koilocytotic atypia were associated with HCIN in 19.2% and 13.7% of cases, respectively. Some subtypes of borderline change are more frequently associated with HCIN. The difference is not sufficient to dictate clinical management.

Cell Nucleus↗

In-vivo non-invasive study of the thermoregulatory function of the blood vessels in the rat tail using magnetic resonance angiography.

In rats, a significant portion of total body heat loss occurs through sympathetically mediated changes in tail blood flow, making the rat tail a convenient model to study vasomotor activity during thermoregulation. Our aim was to perform a non-invasive study of the mechanisms of blood vessel control in the rat tail upon increasing body temperature. In anaesthetized rats, blood vessel temperature was monitored using non-invasive thermistors positioned on the skin surface, covering the ventral artery (Ta) and lateral vein (Tv), and changes in blood vessel size were measured using in-vivo magnetic resonance angiography (MRA). Two important regions of the tail (base and middle) were studied during a gradual rise of rectal temperature (Tr) from 37 to 40 degrees C. MRA data show that increasing Tr causes increased diameter of both arteries and veins of the tail, that venous diameter changes are greater than arterial diameter changes, and that diameter changes of both types of vessel are greater at the base of the tail than in the middle. Temperature data allowed calculation of (Ta - Tv), which we used as an index of flow through arteriovenous anastomoses (AVAs). The data suggest that AVAs near the base of the tail are important in heat exchange, and that they remain open only for Tr values between 38 and 39 degrees C.

Animals↗

Thrombocytopenia caused by the development of antibodies to thrombopoietin.

Thrombocytopenia developed in some individuals treated with a recombinant thrombopoietin (TPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). Three of the subjects who developed severe thrombocytopenia were analyzed in detail to determine the cause of their thrombocytopenia. Except for easy bruising and heavy menses, none of these subjects had major bleeding episodes; none responded to intravenous immunoglobulin or prednisone. Bone marrow examination revealed a marked reduction in megakaryocytes. All 3 thrombocytopenic subjects had antibody to PEG-rHuMGDF that cross-reacted with endogenous TPO and neutralized its biological activity. All anti-TPO antibodies were immunoglobulin G (IgG), with increased amounts of IgG4; no IgM antibodies to TPO were detected at any time. A quantitative assay for IgG antibody to TPO was developed and showed that the antibody concentration varied inversely with the platelet count. Anti-TPO antibody recognized epitopes located in the first 163 amino acids of TPO and prevented TPO from binding to its receptor. In 2 subjects, endogenous TPO levels were elevated, but the TPO circulated as a biologically inactive immune complex with anti-TPO IgG; the endogenous TPO in these complexes had an apparent molecular weight of 95 000, slightly larger than the full-length recombinant TPO. None of the subjects had atypical HLA or platelet antigens, and the TPO cDNA was normal in both that were sequenced. Treatment of one subject with cyclosporine eliminated the antibody and normalized the platelet count. These data demonstrate a new mechanism for thrombocytopenia in which antibody develops to TPO; because endogenous TPO is produced constitutively, thrombocytopenia ensues.

Adult↗

PDGF-regulated rab4-dependent recycling of alphavbeta3 integrin from early endosomes is necessary for cell adhesion and spreading.

BACKGROUND: It has been postulated that the regulation of integrin vesicular traffic facilitates cell migration by internalizing integrins at the rear of the cell and transporting them forward within vesicles for exocytosis at the leading edge to form new contacts with the extracellular matrix. The rab family of GTPases control key targeting events in the endo/exocytic pathway; therefore, these GTPases may be involved in the regulation of cell-matrix contact assembly. RESULTS: The endo/exocytic cycle of alphavbeta3 and alpha5beta1 integrins was studied using mouse 3T3 fibroblast cell lines. In serum-starved cells, internalized integrins were transported through rab4-positive, early endosomes and arrived at the rab11-positive, perinuclear recycling compartment approximately 30 min after endocytosis. From the recycling compartment, integrins were recycled to the plasma membrane in a rab11-dependent fashion. Following treatment with PDGF, alphavbeta3 integrin, but not alpha5beta1, was rapidly recycled directly back to the plasma membrane from the early endosomes via a rab4-dependent mechanism without the involvement of rab11. This rapid recycling pathway directed alphavbeta3 to numerous small puncta distributed evenly across the dorsal surface of the cell, and the integrin only became localized into focal complexes at later times following PDGF addition. Interestingly, inhibition of PDGF-stimulated alphavbeta3 recycling using dominant-negative rab4 mutants compromised cell adhesion and spreading on vitronectin (a ligand for alphavbeta3), but adhesion to fibronectin (a ligand for alpha5beta1 and alphavbeta3) was unchanged. CONCLUSIONS: We propose that growth factor-regulated, rab4-dependent recycling of alphavbeta3 integrin from early endosomes to the plasma membrane is a critical upstream event in the assembly of cell-matrix contacts.

3T3 Cells↗

A multicenter, matched case-control study of risk factors for equine laminitis.

Risk factors for equine laminitis were examined in a prospective case-control study of the 258 cases seen at six collaborating veterinary teaching hospitals over a 32-month period. Case-control pairs were matched on institution, clinician, and season of diagnosis. The 90% of case-control pairs (78 acute, 155 chronic) that had complete data for age, gender, and breed were used in separate conditional logistic-regression models for acute and chronic laminitis. There was an increase in risk for horses with acute laminitis from 5 to 7 years of age (OR 4.7, 95% CI 1.3-16) and from 13 to 31 years of age (OR 3.9, 95% CI 1.3-12) (both compared to <5 years); risk was increased for chronic laminitis from 10 to 14 years (OR 3, 95% CI 1.4-6.8) and from 15 to 38 years (OR 2.9, 95% CI 1.4-6.1) (both compared to <6 years). Mares - but not stallions - were more likely than geldings to develop acute laminitis (OR 2.6, 95% CI 1.1-6.2) and chronic laminitis (OR 2.0, 95% CI 1.1-3.6). In the small acute-laminitis data set, the breed variable was collapsed into three categories: Thoroughbred (THB, reference), the Quarter Horse (QH), and other (non-QH-THB). The non-QH-THB group was at increased risk of acute laminitis (OR 3.8, 95% CI 1.2-11.8). For the seven breed-group categories used in the chronic-laminitis model, however, all non-THB breed groups appeared significantly at risk as compared to the THB, with odds ratios ranging from 3.3 (95% CI 1.3-8.30) for the QH to 9.1 (95% CI 2.1-39.3) for ponies.

Acute Disease↗

Intracranial injection of recombinant adeno-associated virus improves cognitive function in a murine model of mucopolysaccharidosis type VII.

Mucopolysaccharidosis type VII (MPS VII) is a lysosomal storage disease caused by the lack of beta-glucuronidase (GUSB) activity. GUSB deficiency leads to the progressive accumulation of undegraded glycosaminoglycans (GAGs) in cells of most tissues, including the brain, and is associated with mental retardation. Reduction of lysosomal storage in the central nervous system and prevention of cognitive dysfunction may require intracranial delivery of a therapeutic agent during the newborn period that provides a continuous source of GUSB. Therefore, we injected recombinant adeno-associated virus encoding human GUSB into both the anterior cortex and the hippocampus of newborn MPS VII mice. Total GUSB activity in the brain approached normal levels by 18 weeks. Although GUSB activity was concentrated near the injection sites, lysosomal distension was reduced in most areas of the brain. In addition to histopathologic evidence of GAG reduction, the previously undescribed accumulation of GM2 and GM3 gangliosides in the brain was also prevented. Furthermore, GUSB expression and reduced lysosomal distension correlated with improvements in cognitive function as measured in the Morris Water Maze test. These findings indicate that localized overexpression of GUSB has positive effects on the pathology and cognitive function and does not have overt toxicity.

Animals↗

Just before the Beagle: Charles Darwin's geological fieldwork in Wales, summer 1831.

Darwin returned to Shrewsbury in mid-June 1831 and spent that summer learning geology. He made geological maps of Shropshire and visited Llanymynech and other localities. From 3-20th August he joined Sedgwick on his tour of North Wales; they geologised west of Shrewsbury before travelling through Llangollen, Ruthin, Conwy to Bangor finally reaching Anglesey. Darwin left Sedgwick at Menai and walked to Barmouth making a special visit of Cwm Idwal. He returned to Shrewsbury on 29th August to open the letter from Fitzroy inviting him to join the Beagle. During this summer Darwin gained skills in all aspects of geology, including chemical analysis, which were to prove vital in the development of his ideas on natural selection.

Biology↗