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Biomedical subjects

N Smith

Publications and source records attributed to N Smith.

At least 55 records · Page 3Linked to original sources
PubMed2001

Intraspecific phylogeography of Lacerta vivipara and the evolution of viviparity.

The lacertid lizard Lacerta vivipara is one of the few squamate species with two reproductive modes. We present the intraspecific phylogeny obtained from neighbor-joining and maximum-parsimony analyses of the mtDNA cytochrome b sequences for 15 individuals from Slovenian oviparous populations, 34 individuals from western oviparous populations of southern France and northern Spain, 92 specimens from European and Russian viviparous populations, and 3 specimens of the viviparous subspecies L. v. pannonica. The phylogeny indicates that the evolutionary transition from oviparity to viviparity probably occurred once in L. vivipara. The western oviparous group from Spain and southern France is phylogenetically most closely related to the viviparous clade. However, the biarmed W chromosome characterizing the western viviparous populations is an apomorphic character, whereas the uniarmed W chromosome, existing both in the western oviparous populations and in the geographically distant eastern viviparous populations, is a plesiomorphic character. This suggests an eastern origin of viviparity. Various estimates suggest that the oviparous and viviparous clades of L. vivipara split during the Pleistocene. Our results are discussed in the framework of general evolutionary models: the concept of an oviparity-viviparity continuum in squamates, the cold climate model of selection for viviparity in squamates, and the contraction-expansion of ranges in the Pleistocene resulting in allopatric differentiation.

Animals↗
PubMed2001

Developmental expression of the tuberous sclerosis proteins tuberin and hamartin.

Tuberous sclerosis complex is an autosomal dominant multisystem disorder, characterized by the development of hamartomas in multiple organs, primarily the skin, heart, kidney, and brain. The tuberous sclerosis genes, TSC1 and TSC2, encode hamartin and tuberin, respectively. Employing specific antibodies for hamartin and tuberin, we analyzed the expression of these two proteins by Western blot analyses in normal developing human and rat tissues. Both proteins are expressed ubiquitously in human fetal tissues and placenta, but are expressed at relatively low levels in human adult tissues, except brain. Similarly, high expression of these two proteins is observed in rat embryonic tissues, with a progressive decline after birth. To better characterize the developmental expression of tuberin and hamartin, we conducted a detailed study in rat tissues from embryonic day 13 to adult by Western blot analysis and immunohistochemistry. Immunohistochemical staining of rat tissues for tuberin and hamartin revealed tissue-specific expression patterns throughout development. Both tuberin and hamartin are expressed in epithelia, muscle (smooth, cardiac and skeletal muscle) and the nervous system (neurons, glia, choroid plexus and arachnoid). Except for the central nervous system, immunostaining intensity declines with age, confirming the protein blot analysis. These results indicate that tuberin and hamartin may play a critical role in development, and thus provide a framework for understanding the developmental and hamartomatous manifestations of tuberous sclerosis. These findings also suggest that tuberin and hamartin have additional functions in the adult brain, consistent with the marked neurological problems that afflict many patients with tuberous sclerosis.

Age Factors↗
PubMed2001

Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes.

Ineffectual wound healing in hyperglycaemic patients suffering from diabetes mellitus is characterised by a reduction in capillary reformation (angiogenesis). Basic fibroblast growth factor (FGF-2) is secreted by fibroblasts, macrophages and in particular endothelial cells (EC) in response to tissue injury and is important in promotion of neovascularisation. Recently, glycation of FGF-2 has been shown to significantly reduce its activity in vitro. We have examined the kinetics of FGF-2 glycation and compared its ability with that of native FGF-2 to activate mitogenesis, capillary formation and associated signal transduction in bovine aortic EC (BAEC). FGF-2 was exposed to 0.25 M glucose-6-phosphate (G-6-P) for 24-72 h and the degree of glycation determined by matrix assisted laser desorption ionisation mass spectrometry. Native FGF-2 was heterogeneous with Mw in the range 15,153.6-17,903 Da. After 24 h incubation with G-6-P there was evidence of glycation, and the mass increase corresponded to addition of 2.7 mol of G-6-P residues; after 48 h, 4 mol sugar was added and this increased to 8.7 after 72 h. Dimerisation of FGF-2 was observed after 72 h of treatment. Induction of mitogenesis in BAEC was significantly reduced by 25%-40% after treatment for 48-96 h with glycated (24 h) FGF-2 (gFGF-2; 100 pg/ml-5 ng/ml; P < 0.05), whilst capillary tubule formation was significantly reduced by between 60% and 90% (100 pg/ml-1 ng/ml; P < 0.05) after 5 days compared to native FGF-2. Subsequent investigation of the signal transduction molecules associated with mitogenesis showed a reduction in FGF-2 induced tyrosine phosphorylated proteins of approximate Mw 20-150 kDa between 10 min and 24 h, in particular, mitogen activated protein kinase (MAPK)/early response kinase (ERK-1, ERK-2), after glycation. To determine the reason for reduced angiogenic activity of gFGF-2, we compared its binding characteristics to that of native FGF-2. Total binding of gFGF-2 to the cell surface was significantly reduced in BAEC analysed by FACS compared to native FGF-2 (P < 0.05). Further investigation using 125I-labelled differentially washed samples, demonstrated a significant reduction in gFGF-2 binding to the high affinity tyrosine kinase receptor (46%) compared to native FGF-2. In summary, glycation of FGF-2 in vitro occurs rapidly within 24 h in the presence of elevated levels of G-6-P. Glycation caused a significant reduction in the ability of FGF-2 to bind to the tyrosine kinase receptor and activate signal transduction pathways responsible for both mitogenesis and capillary formation in BAEC. These results could help to explain the mechanism behind impaired wound healing in patients with diabetes mellitus.

Animals↗
PubMed2001

Altered megakaryocyte-platelet haemostatic axis in hypercholesterolaemia.

Hypercholesterolaemia is associated with accentuated platelet function. We assessed in a pilot study whether megakaryocytes (MK), the platelet precursor cell, were altered in subjects with primary hypercholesterolaemia and whether these changes were linked with platelet function. MK and platelet function were assessed in eight untreated patients with primary hypercholesterolaemia (total cholesterol, TC > 7 mmol/l), and 14 control subjects (TC < or = 7 mmol/l): MK ploidy (DNA content), size, granularity, and expression of the adhesion molecule GP IIIa, and platelet expression of GP IIIa, P selectin and CD 63, and RNA content, were each measured using flow cytometry; mean platelet volume, platelet count, plasma thrombopoietin, and cutaneous bleeding time were also assessed. Hypercholesterolaemic patients had increased MK ploidy, mean (SD) 22.9 N (2.3) vs. 20.8 N (1.6) (2P=0.021); platelet size, 10.6 fl (1.2) vs. 9.3 fl (0.7) (2P=0.006); and platelet expression of GP IIIa, 111.3 (18.9) vs. 92.0 (12.3) (2P=0.010), as compared with matched control subjects. Cutaneous bleeding time tended to be reduced in the hypercholesterolaemic patients, 364 s (136) vs. 483 s (165) (2P=0.11). No differences in MK size, granularity or GP IIIa expression, or platelet count, mass, RNA content, P selectin or CD 63 expression, or plasma thrombopoietin were seen. The data suggest that aspects of megakaryocytes and platelets are altered in hypercholesterolaemia, as has also been seen in other vascular risk factors states, including hypertension and diabetes mellitus. Furthermore, changes in megakaryocytes may have contributed to the altered platelet function seen here. Further study is now required to assess whether lipid lowering therapy "normalises" these changes in the megakaryocyte-platelet haemostatic axis.

Adult↗
PubMed2001

Breathing patterns and aerosol delivery: impact of regular human patterns, and sine and square waveforms on rate of delivery.

In vitro tests are commonly employed to assess nebulizer performance. Whether the square or sine waveforms employed during in vitro tests could alter the nebulizer performance compared to that observed when a patient breathes through the nebulizer is debatable. Accordingly, the aim of this in vitro study was to compare the rates of delivery from nebulizers with simulated human breathing patterns to those obtained with matching sine and square waveforms. Regular human breathing patterns with tidal volumes (VT) of approximately 40, approximately 200, approximately 500, and approximately 800 mL were selected. Sine and square waveforms that matched the VT, peak inspiratory flow rate (PIF), breathing frequency (f), and inspiratory duty cycle (t(i)/t(tot)) of the human breathing patterns were created with a breathing simulator. The rate of delivery of nebulized technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTC-DTPA) from two different jet nebulizer brands was determined. The rate of delivery was defined as the amount of the 99mTC-DTPA deposited during 30 sec of nebulization on a filter placed between the nebulizer and the breathing simulator. The rate of delivery of 99mTC-DTPA with the human breathing pattern was similar to that measured with the matching sine or square waveforms for either nebulizer. The configuration of the breath (PIF, VT, f, t(i)/t(tot)) did, however, influence the rate of delivery. In conclusion, the shape of the waveform, in other words, one resulting from a human breathing pattern, or a matching sine or square waveform, did not influence the rate of 99mTC-DTPA delivery from a nebulizer in vitro.

Aerosols↗
PubMed2000

Long-term survival of hamster hearts in presensitized rats.

We transplanted hamster hearts into rats that had been sensitized to hamster cardiac grafts 5 days earlier as a model for discordant xenotransplantation. Sensitized rats had high serum levels of elicited anti-donor IgM and IgG that caused hyperacute rejection. Transient complement inhibition with cobra venom factor (CVF) plus daily and continuing cyclosporin A (CyA) prevented hyperacute rejection. However, grafts underwent delayed xenograft rejection (DXR). DXR involved IgG and associated Ab-dependent cell-mediated rejection, because depletion of IgG or Ab-dependent cell-mediated rejection-associated effector cells prolonged graft survival and the serum-mediated Ab-dependent cell-mediated cytotoxicity in vitro. Blood exchange in combination with CVF/CyA treatment dramatically decreased the level of preexisting Abs, but DXR still occurred in association with the return of Abs. Splenectomy and cyclophosphamide acted synergistically to delay Ab return, and when combined with blood exchange/CVF/CyA facilitated long-term survival of grafts. These grafts survived in the presence of anti-donor IgM, IgG, and complement that precipitated rejection of naive hearts, indicating that accommodation (survival in the presence of anti-graft Abs and complement) had occurred. We attribute the long-term survival to the removal of preexisting anti-donor Abs and therapy that attenuated the rate of Ab return. Under such conditions, the surviving hearts showed expression in endothelial cells and smooth muscle cells of protective genes and an intragraft Th2 immune response. Th2 responses and protective genes are associated with resistance to IgM- and IgG-mediated, complement-dependent and -independent forms of rejection.

Animals↗
PubMed2000

Large-Scale Structure of the Carina Nebula.

Observations obtained with the Midcourse Space Experiment (MSX) satellite reveal for the first time the complex mid-infrared morphology of the entire Carina Nebula (NGC 3372). On the largest size scale of approximately 100 pc, the thermal infrared emission from the giant H ii region delineates one coherent structure: a (somewhat distorted) bipolar nebula with the major axis perpendicular to the Galactic plane. The Carina Nebula is usually described as an evolved H ii region that is no longer actively forming stars, clearing away the last vestiges of its natal molecular cloud. However, the MSX observations presented here reveal numerous embedded infrared sources that are good candidates for sites of current star formation. Several compact infrared sources are located at the heads of dust pillars or in dark globules behind ionization fronts. Because their morphology suggests a strong interaction with the peculiar collection of massive stars in the nebula, we speculate that these new infrared sources may be sites of triggered star formation in NGC 3372.

Journal Article↗
PubMed2000

eta Carinae: Testing a Binary Orbit Model with the Hubble Space Telescope/Space Telescope Imaging Spectrograph.

Ground-based spectroscopy of eta Car shows periodic changes in some emission-line wavelengths. These variations have been cited as strong evidence that this object is a 5.5 yr binary system and have been used to produce specific orbit models. High spatial resolution data obtained with the Hubble Space Telescope/Space Telescope Imaging Spectrograph, however, do not confirm the predicted velocity behavior; therefore, the published orbit models are almost certainly invalid. Wavelength fluctuations seen at ground-based spatial resolution most likely result from other effects, which we describe. If this object is a binary system (which has not been proven), then the parameters of the secondary star and of the orbit remain largely unknown.

Journal Article↗
PubMed2000

Recent Changes in the Near-Infrared Structure of eta Carinae.

Near-infrared imaging at two phases in the 5 yr spectroscopic cycle of eta Carinae reveals changes in the spatial structure of the inner core that may be related to recently reported near-infrared photometric variability. The central source changed from a pointlike object to a more extended, bipolar or shell structure. This behavior is reminiscent of changes observed in the radio continuum. NICMOS images show a toroidal distribution of dust and gas around the central star and confirm the morphology of several other structures observed in ground-based images of the Homunculus. The morphological variations appear to be confined to the central core of the nebula.

Journal Article↗
PubMed2000

Randomised controlled trial comparing effectiveness of touch screen system with leaflet for providing women with information on prenatal tests.

OBJECTIVE: To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests. DESIGN: Randomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only). SETTING: Antenatal clinic in university teaching hospital. SUBJECTS: 875 women booking antenatal care. INTERVENTIONS: All participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic. MAIN OUTCOME MEASURES: Women's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety. RESULTS: All women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001). CONCLUSIONS: The touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy.

Attitude to Health↗
PubMed2000

Theory and practice in sport psychology and motor behaviour needs to be constrained by integrative modelling of brain and behaviour.

Because of advances in technology, the non-invasive study of the human brain has enhanced the knowledge base within the neurosciences, resulting in an increased impact on the psychological study of human behaviour. We argue that application of this knowledge base should be considered in theoretical modelling within sport psychology and motor behaviour alongside existing ideas. We propose that interventions founded on current theoretical and empirical understanding in both psychology and the neurosciences may ultimately lead to greater benefits for athletes during practice and performance. As vehicles for exploring the arguments of a greater integration of psychology and neurosciences research, imagery and perception-action within the sport psychology and motor behaviour domains will serve as exemplars. Current neuroscience evidence will be discussed in relation to theoretical developments; the implications for sport scientists will be considered.

Behavior↗
PubMed2000

An epidemiological study to establish the prevalence of urinary symptoms and felt need in the community: the Leicestershire MRC Incontinence Study. Leicestershire MRC Incontinence Study Team.

BACKGROUND: The aim of the study was to establish the prevalence of urinary symptoms and felt need in adults. This paper discusses problems with setting thresholds to distinguish cases from non-cases in this field of research. Few studies have provided detailed age- and sex-specific prevalence estimates for felt need in relation to urinary symptoms. METHODS: A cross-sectional postal survey was carried out of 15,904 community-dwelling adults aged 40 years or more registered with general practitioners in Leicestershire. Subjects were selected randomly by household from the Leicestershire Health Authority Register. The postal questionnaire consisted of questions on general health, urinary and bowel symptoms, quality of life, service use and demographic characteristics. RESULTS: Thirty-four per cent of the sample reported clinically significant symptoms. The prevalence and severity of symptoms increased with age. However, only 2 per cent of the sample reported symptoms that were clinically significant, bothersome and socially disabling. CONCLUSION: Urinary symptoms are very common in adults over 40 years of age living in the community. However, symptom-based estimates probably overestimate the level of need for health care in the community. It may be more effective and efficient to target services, in the first instance, on those people who report clinically significant symptoms that are bothersome or socially disabling. A consensus on thresholds and definitions of urinary symptoms is required to standardize clinical and research work and to target services more appropriately.

Adult↗