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Biomedical subjects

D Lees

Publications and source records attributed to D Lees.

At least 19 recordsLinked to original sources
PubMed2000

Viruses and bivalve shellfish.

The epidemiological data clearly demonstrates that filter feeding bivalve shellfish can, and do, act as efficient vehicles for the transmission of enteric viruses transmitted by the faecal-oral route. This identified hazard has been documented as a cause for concern by various international agencies and has a long history. Disease outbreaks can occur on an epidemic scale as graphically illustrated by an outbreak of Hepatitis A in Shanghai, China in 1988 involving about 300,000 cases. Improvement of harvesting area water quality offers the most sustainable route to improvement in the virological quality of bivalve shellfish sold live. However there is growing awareness, and concern, that current regulatory standards based on faecal coliform monitoring do not fully protect the shellfish consumer from viral infection. New viral test methods based on PCR, and the development of alternative more reliable faecal pollution indicators, offer new approaches for the further development of public health controls. However, further work is required to build a scientific consensus and to understand the implications of their introduction into legislation.

Adenoviridae↗
PubMed1996

An hypothesis for the interpretation of the contractile response of vascular smooth muscle at the cellular level.

The long preservation and recovery of functional (contractile) properties in cultured aortic smooth muscle cells, even after replating or deep-frozen storage and the measurement of their responses are now technically settled issues. We could thus study extensively the responses of single cultured cells from rat thoracic aorta. Responses were elicited by the addition of KCl 40 mmol/L without or with a calcium blocker PN 200-100 (10(-6) mol/L); angiotensin II (10(-11)-10(-6) mol/L) without or with antagonist (losartan 10(-5) mol/L); or serotonin (10(-9)-10(-4) mol/L) without or with antagonist (naftidrofuryl 10(-5) mol/L). Results thus obtained enabled us to propose a new hypothesis for the interpretation of the contractile responses of an elastic vascular smooth muscle. The different maximal effects of different agonists result mainly from the different proportions of cells they can mobilize; the agonist concentration-contraction relationship is mainly due to the increase of the proportion of cells involved up to a maximal value typical of the agonist used. An antagonist primarily reduce the proportion of cells an agonist can mobilize. Some of the consequences of this hypothesis are briefly outlined.

Angiotensin II↗
PubMed1995

Parallel expression level of dystrophin and contractile performances of rat aortic smooth muscle.

We have recently shown that the expression of dystrophin was in line with the conservation of contractility in primary and subcultured vascular smooth muscle cells (VSMC). In this report, we provide experimental evidence that shows the existence of a gradient in dystrophin expression from the aortic arch to the region just above the diaphragm, in line with a parallel gradient of contractility. On the contrary, there were no differences in caldesmon and smooth muscle myosin expression, as previously shown for vimentin and alpha-smooth muscle actin [Osborn, M., Caselitz, J., and Weber, K. (1981) Differentiation 20, 196-202]. Overall, this is the first demonstration, in a normal adult smooth muscle, of a differential expression of dystrophin, in line with its contractile performances. In addition, these results suggest that the experimental modulation of dystrophin expression in cultured VSMC in line with their contractility was the manifestation in vitro of an actual physiological property of those cells in vivo.

Actins↗
PubMed1994

Dystrophin does not influence regular cytoskeletal architecture but is required for contractile performance in smooth muscle aortic cells.

Cultured vascular smooth muscle cells express distinct histological phenotypes due to a contractile to synthetic stage transition. In this study, we compared the behaviour of cultured aortic smooth muscle cells from young normal and mdx mice. Morphological, immunobiochemical, immunocytochemical analyses and contraction studies of these cells demonstrated that (i) the cell cytoskeleton in mdx mice is not affected by the absence of dystrophin since proteins such as caldesmon, a-actin, and vinculin are expressed similarly in normal mice, (ii) utrophin (or dystrophin-related protein) overexpression does not compensate for the physiological and functional role of the lacking dystrophin. These data suggested that dystrophin and utrophin cannot substitute one another and may play different or complementary roles within smooth muscle cells.

Animals↗
PubMed1994

Dystrophin (Xp21), a new phenotype marker of cultured rat aortic myocytes.

Dystrophin is a low-abundance cytoskeletal protein involved in the maintenance of membrane integrity in striated muscle. Very little is known about its role in smooth muscle. Utrophin (a dystrophin-related protein) is an ubiquitous protein whose role is still unclear. Changes in the expression of both proteins (if any) during phenotypic modulation of smooth muscle have not yet been reported. In contrast, modulated expression of heavy-molecular-weight caldesmon (h-CaD), a well-known specific regulatory protein of the contractile apparatus in smooth muscle, is well documented, along with its nonmuscle isoform, low-molecular-weight caldesmon (1-CaD), and other cytoskeletal proteins. We investigated three properties of cultured rat aortic smooth muscle cells: morphology, contractile ability, and expression of dystrophin, utrophin, h-CaD, and 1-CaD. Cells were grown either in serum substitute supplemented medium (U-medium), where they reexpressed contractility, or in fetal calf serum-supplemented medium (F-medium), where they did not. It was found that only cultures grown in U-medium continued expressing dystrophin, even during the proliferation phase, contrary to cells grown in F-medium. However, when F-medium was changed for U-medium the cells recovered their contractility and reexpressed dystrophin. Expression of utrophin, h-CaD, and 1-CaD was similar in both culture types. Dystrophin was demonstrated to be a true phenotype marker of cultured rat aortic smooth muscle cells, particularly with respect to their actual contractility.

Animals↗
PubMed1994

A simple method for the quantitative evaluation of functional effects of xenobiotics with cultured cells.

We present a simple, noninvasive, nondestructive all-purpose method for the quantitative evaluation of functional effects of xenobiotics with cultured cells and the work station for its routine, easy implementation. At present 1 to 150 cells growing in one to six dishes can be studied in parallel or otherwise at time intervals ranging from 10 s to 6 h or more, over periods of time ranging from a few tens of minutes to 3-4 days. Any aspect of cell physiological behavior can be studied (differentiation-dedifferentiation, migration, division, degeneration, death) without preliminary staining and/or fixation provided it results in optically visible changes.

Animals↗
PubMed1994

Effects of isoflurane on regional coronary blood flow and myocardial tissue pressure in chronically instrumented dogs.

BACKGROUND: The effects of isoflurane on distribution of transmural blood flow and transmural intramyocardial tissue pressure (IMP) were studied in chronically instrumented dogs, to address following aims: (1) to evaluate the direct effects of isoflurane on transmural blood flow distribution in the absence of compounding effects of baseline anesthetics, acute surgery, and indirect effects caused by changes in systemic blood pressures and heart rate--factors that were not well controlled in the past studies; (2) to examine the relation between transmural myocardial perfusion pressure and concurrent changes in transmural blood flow distribution during isoflurane anesthesia; and (3) to evaluate the effects of isoflurane on transmural myocardial oxygen supply-demand relation. METHODS: Dogs were allowed to recover at least 1 week after surgery for instrumentation. Blood flow of the left anterior descending coronary artery and subendocardial and subepicardial blood flows, regional IMPs, regional segmental dimension, heart rate, aortic pressure and left ventricular pressure were measured while dogs were awake and during 1.3% isoflurane anesthesia, with and without correction of heart rate and aortic pressure. Concurrently regional myocardial perfusion pressure, regional myocardial stroke work, and systolic pressure time index were calculated, based on direct measurements of IMP in subendocardium and subepicardium. RESULTS: Without correction of aortic pressure, neither left anterior descending coronary artery flow nor transmural blood flow distribution was altered with isoflurane. When aortic pressure and heart rate were corrected to the awake values, left anterior descending coronary artery flow increased (37 +/- 2%) and the increase was preferentially distributed to subendocardium, resulting in a shift in transmural blood flow. The subendocardial/subepicardial blood flow ratio increased from 1.2 +/- 0.3 to 1.4 +/- 0.4 (p, 0.05). The transmural blood flow changes were closely related to changes in regional myocardial perfusion pressure ratio between subendocardium and subepicardium (r = 0.76, P < 0.001). Concurrent with marked increases in blood flow (55 +/- 4% increase), regional myocardial stroke work and systolic pressure time index of subendocardium were decreased more than 50% with isoflurane, resulting in a favorable subendocardial oxygen supply-demand balance. CONCLUSIONS: Isoflurane is a coronary vasodilator and redistributes blood flow in favor of subendocardium and depresses subendocardial work when heart rate and aortic pressure are controlled. These changes in regional myocardial blood flow, regional myocardial stroke work, and systolic pressure time index appear to be a result of changes in regional IMP.

Animals↗
PubMed1994

Will robots ever replace attendants? Exploring the current capabilities and future potential of robots in education and rehabilitation.

This article describes the current capabilities and future potential of robots designed as supplements or replacements for human assistants or as tools for education and rehabilitation. A number of researchers have developed and tested a variety of robot assistants for individuals with disabilities. These robots can usually be classified as educational, vocational or independent-living assistants. Robots in all three categories are reviewed. A brief summary of the critical characteristics of human service robots is also presented and the limitations of current technology are discussed. Finally, current research aimed at addressing these limitations is described. White robots of all kinds have proven much more difficult to develop than people had expected, we conclude that it will eventually be possible to create an effective, reliable robot for human service tasks, but not as quickly as was predicted in the early 1980s.

Activities of Daily Living↗
PubMed1993

Results with OECD recommended positive control sensitizers in the maximization, Buehler and local lymph node assays.

The guinea pig maximization test and the Buehler occluded patch test are used widely to identify the sensitization potential of new chemicals. This information enables toxicologists and/or regulatory authorities to determine whether a chemical should be classified formally as a skin sensitizer. Both to improve and to harmonize these assessments internationally, the OECD has recommended recently that moderate rather than strong contact sensitizers are used as positive control substances. The purpose is to ensure an adequate level of sensitivity in sensitization assays performed at specific testing establishments. Results from two laboratories reported here show that the minimum acceptable standard laid down by the OECD can be achieved and indeed commonly exceeded by a substantial margin. Furthermore, results with these positive controls in a new method, the local lymph node assay, also appear to satisfy similar criteria, suggesting results from this assay, including negative data, should be acceptable for classification purposes. However, a review of the way in which results with new chemicals will be interpreted for regulatory purposes, in the context of positive control data, reveals that considerable inadequacies still exist. It is recommended that ultimately, sensitization data can only be interpreted meaningfully (i.e. to protect humans from sensitization hazards) by considering the potency of the contact allergen in the context of the sensitivity of the assay performed at the particular testing institution.

Acrolein↗
PubMed1993

Cytokine gene expression in human multiple myeloma.

In the present study the gene expression of cytokines promoting in vitro myeloma-cell growth was investigated by Northern blot analysis using total RNA of 36 tumour samples of patients with multiple myeloma (MM) or plasma cell leukaemia and poly(A)+ RNA of 10 human myeloma cell lines (HMCL). These cytokines included interleukin (IL)-1 alpha, IL-1 beta, IL-3, IL-6, granulocyte-macrophage (GM)-colony-stimulating factor (CSF) and granulocyte (G)-CSF. IL-1 beta, IL-6 and G-CSF genes were coexpressed in most patients, although at variable levels. IL-1 alpha transcripts were detected in 32% of patients in whom coexpression of IL-1 beta gene was found. IL-3 gene was not expressed in patients' cells and GM-CSF mRNA was detected in only 1/32 patients. No detectable transcripts for the above cytokines were present in HMCL, whereas IL-6 gene was expressed in 2/10 HMCL. We also looked for the presence of transcripts for IL-2, leukaemia inhibitory factor (LIF) and transforming growth factor (TGF)beta in cells of tumour samples from the same patients and in HMCL. IL-2 gene was not expressed in MM patients and HMCL. Weak expression of LIF gene was detected in three patients (9%), and transforming growth factor beta (TGF beta) mRNA was observed in 12/12 tumour samples analysed and all HMCL. These results suggest that, among cytokines shown to control myeloma-cell growth in vitro, IL-1, IL-6 and G-CSF could play a role in the development of myeloma disease in vivo.

Blotting, Northern↗
PubMed1992

Up-regulation of interleukin (IL)-6 receptor gene expression in vitro and in vivo in IL-6 deprived myeloma cells.

Myeloma cells absolutely require interleukin-6 (IL-6) for growing in vivo in patients with multiple myeloma and exogenous IL-6-dependent myeloma cell lines have been reproducibly obtained. In this study we show a dramatic up-regulation of the IL-6 receptor (gp80 chain) gene expression in myeloma cell lines following the removal of exogenous IL-6. Such a regulation was also known to occur in IL-6-deprived myeloma cells in vivo in three patients who were treated with optimal doses of anti-IL-6 monoclonal antibodies. The direct effect of IL-6 on IL-6 receptor gene expression in myeloma cells was further confirmed by adding IL-6 to an autonomously growing myeloma cell line.

Blotting, Northern↗
PubMed1991

Mutational analysis of the putative PLA2-inhibiting sequence of annexin 1.

Annexin 1 has been proposed to inhibit phospholipase A2 by direct interaction through a specific amino acid sequence spanning residues 246-254. The possible role of this region was investigated by protein engineering. Three point mutations and a deletion have been performed. The four mutant proteins have been expressed in E. coli, purified and tested for calcium and lipid binding, and for phospholipase inhibition. All mutant proteins conserved the properties of the wild-type recombinant protein. This result clearly demonstrates that this part of the molecule is not involve in the inhibition of phospholipase A2.

Amino Acid Sequence↗
PubMed1991

Assessment of the relative skin sensitizing potency of 3 biocides using the murine local lymph node assay.

The relative skin-sensitizing potency of 3 biocides, 5-chloro-2-methyl-4-isothiazolin-3-one (the major active ingredient in Kathon CG), 1,2-benzisothiazolin-3-one and 2-methyl-4,5-trimethylene-4-isothiazolin-3-one, was assessed using the murine local lymph node assay. Potency was ranked according to the lowest dose of material which, following epicutaneous exposure, induced a significant proliferation of T lymphocytes in the draining lymph nodes. The results showed that 5-chloro-2-methyl-4-isothiazolin-3-one was able to induce proliferative activity at significantly lower dose levels than the other 2 biocides and that it may therefore be a more potent skin sensitizer.

Animals↗
PubMed1989

Clinical evaluation of a desktop robotic assistant.

A desktop vocational assistant robotic workstation was evaluated by 24 high-level quadriplegics from the Palo Alto Veterans Affairs Spinal Cord Injury Center. The system is capable of performing daily living and vocational activities for individuals with high-level quadriplegia via voice control. Subjects were asked to use the robot to perform a repertoire of daily living activities, including preparing a meal and feeding themselves, washing their face, shaving, and brushing teeth. Pre- and post-test questionnaires, interviews, and observer assessments were conducted to determine the quality of the robot performance and the reaction of the disabled users toward this technology. Results of the evaluations were generally positive and demonstrated the usefulness of this technology in assisting high-level quadriplegics to perform daily activities and to gain a modicum of independence and privacy in their lives.

Activities of Daily Living↗
PubMed1986

Endobronchial metastases from soft tissue sarcoma.

The majority of patients with pulmonary metastases from primary soft tissue sarcomas have peripheral lesions that can be removed by wedge excision. A subset of these patients, however, present with, or develop, clinically significant endobronchial metastases. These patients require a preoperative evaluation that includes pulmonary function testing and a detailed endoscopic evaluation of the bronchial tree. We described three of these patients from the National Cancer Institute and review the clinical histories of eight additional previously reported cases.

Adult↗