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Biomedical subjects

John Gamble

Publications and source records attributed to John Gamble.

10 recordsLinked to original sources
PubMed2006

EMBL Nucleotide Sequence Database: developments in 2005.

The EMBL Nucleotide Sequence Database (www.ebi.ac.uk/embl) at the EMBL European Bioinformatics Institute, UK, offers a comprehensive set of publicly available nucleotide sequence and annotation, freely accessible to all. Maintained in collaboration with partners DDBJ and GenBank, coverage includes whole genome sequencing project data, directly submitted sequence, sequence recorded in support of patent applications and much more. The database continues to offer submission tools, data retrieval facilities and user support. In 2005, the volume of data offered has continued to grow exponentially. In addition to the newly presented data, the database encompasses a range of new data types generated by novel technologies, offers enhanced presentation and searchability of the data and has greater integration with other data resources offered at the EBI and elsewhere. In stride with these developing data types, the database has continued to develop submission and retrieval tools to maximise the information content of submitted data and to offer the simplest possible submission routes for data producers. New developments, the submission process, data retrieval and access to support are presented in this paper, along with links to sources of further information.

Animals↗
PubMed2006

Effect of high altitude and exercise on microvascular parameters in acclimatized subjects.

The role of microvascular fluid shifts in the adaptation to hypobaric hypoxia and its contribution to the pathophysiology of AMS (acute mountain sickness) is unresolved. In a systematic prospective study, we investigated the effects of hypobaric hypoxia and physical exercise alone, and in combination, on microvascular fluid exchange and related factors. We used computer-assisted VCP (venous congestion plethysmography) on the calves of ten altitude-acclimatized volunteers. We investigated the effects of: (i) actively climbing to an altitude of 3196 m, (ii) airlifting these subjects to the same altitude, and (iii) exercise at low altitude. CFC (capillary filtration capacity), Pvi (isovolumetric venous pressure) and Qa (calf blood flow) were assessed before and after each procedure and then repeated after an overnight rest. Measurements of CFC showed no evidence of increased microvascular permeability after any of the procedures. Pvi was significantly decreased (P<0.001) from 20.3+/-4.4 to 8.9+/-4.3 mmHg after active ascent, and was still significantly lower (P=0.009) after overnight rest at high altitude (13.6+/-5.9 mmHg). No such changes were observed after the passive ascent (16.7+/-4.0 mmHg at baseline; 17.3+/-4.5 mmHg after passive ascent; and 19.9+/-5.3 mmHg after overnight rest) or after exercise at low altitude. After the active ascent, Qa was significantly increased. We also found a significant correlation between Qa, Pvi and the number of circulating white blood cells. In conclusion, we found evidence to support the hypothesis that increased microvascular permeability associated with AMS does not occur in acclimatized subjects. We also observed that the microvascular equilibrium pressure (Pvi) fell in inverse relation to the increase in Qa, especially in hypoxic exercise. We hypothesize that this inverse relationship reflects the haemodynamic changes at the microvascular interface, possibly attributable to the flow-induced increases in endothelial surface shear forces.

Acclimatization↗
PubMed2005

The EMBL Nucleotide Sequence Database.

The EMBL Nucleotide Sequence Database (http://www.ebi.ac.uk/embl), maintained at the European Bioinformatics Institute (EBI) near Cambridge, UK, is a comprehensive collection of nucleotide sequences and annotation from available public sources. The database is part of an international collaboration with DDBJ (Japan) and GenBank (USA). Data are exchanged daily between the collaborating institutes to achieve swift synchrony. Webin is the preferred tool for individual submissions of nucleotide sequences, including Third Party Annotation (TPA) and alignments. Automated procedures are provided for submissions from large-scale sequencing projects and data from the European Patent Office. New and updated data records are distributed daily and the whole EMBL Nucleotide Sequence Database is released four times a year. Access to the sequence data is provided via ftp and several WWW interfaces. With the web-based Sequence Retrieval System (SRS) it is also possible to link nucleotide data to other specialist molecular biology databases maintained at the EBI. Other tools are available for sequence similarity searching (e.g. FASTA and BLAST). Changes over the past year include the removal of the sequence length limit, the launch of the EMBLCDSs dataset, extension of the Sequence Version Archive functionality and the revision of quality rules for TPA data.

Base Sequence↗
PubMed2005

A restrospective perspective.

Venous occlusion plethysmography is a simple but elegant technique that has contributed to almost every major area of vascular biology in humans. The general principles of plethysmography were appreciated by the late 1800s, and the application of these principles to measure limb blood flow occurred in the early 1900s. Plethysmography has been instrumental in studying the role of the autonomic nervous system in regulating limb blood flow in humans and important in studying the vasodilator responses to exercise, reactive hyperemia, body heating, and mental stress. It has also been the technique of choice to study how human blood vessels respond to a variety of exogenously administered vasodilators and vasoconstrictors, especially those that act on various autonomic and adrenergic receptors. In recent years, plethysmography has been exploited to study the role of the vascular endothelium in health and disease. Venous occlusion plethysmography is likely to continue to play an important role as investigators seek to understand the physiological significance of newly identified vasoactive factors and how genetic polymorphisms affect the cardiovascular system in humans.

Cardiovascular Diseases↗
PubMed2004

Innate BALB/c enteric epithelial responses to Trichinella spiralis: inducible expression of a novel goblet cell lectin, intelectin-2, and its natural deletion in C57BL/10 mice.

Infection of mice with the nematode parasite Trichinella spiralis induces changes in the proteome of the jejunal epithelium, including substantial up-regulation of a novel variant of interlectin. In this study we sequence this novel lectin, termed intelectin-2, and compare expression levels during T. spiralis infection of resistant (BALB/c) with susceptible (C57BL/10) mouse strains. Intelectin-2 was cloned and sequenced from BALB/c mRNA extracted on day 14 of infection, and was found to have 91% amino acid identity with intelectin (within our study termed intelectin-1). Intelectin-2 transcripts were up-regulated early (day 3) during infection with T. spiralis in BALB/c mice, suggesting an innate response, and levels remained high through to day 14 (time of parasite rejection). Immunohistochemistry of jejunal sections with a rabbit polyclonal Ab to Xenopus laevis 35-kDa cortical granule lectin (XL35; 68% identity with intelectin-2) followed a similar pattern, with intense labeling of goblet and Paneth cells at day 14. However, intelectin-2 transcripts and protein were absent, and immunohistochemistry negative when C57BL/10 mice were infected with T. spiralis. Genomic PCR and Southern blotting confirmed that the intelectin-2 gene is absent from the C57BL/10 genome. The presence of intelectin-2 in resistant BALB/c mice, its absence from the susceptible C57BL/10 strain and the kinetics of its up-regulation during T. spiralis infection suggest that this novel lectin may serve a protective role in the innate immune response to parasite infection.

Amino Acid Sequence↗
PubMed2004

Garlic supplementation increases peripheral blood flow: a role for interleukin-6?

There is considerable epidemiological and clinical evidence that regular garlic supplementation reduces cardiovascular risk. In this study, we have investigated the hypothesis that dietary garlic supplementation increases tissue blood flow and this is mediated by the vasodilatory actions of interleukin-6 (IL-6). Venous occlusion plethysmography was used to measure resting calf blood flow before and after oral administration of 600 mg of garlic tablets once daily for 7 days in 13 young healthy female volunteers (treatment group) and 13 female controls matched for age and body mass index (BMI). Blood samples were obtained at the time of plethysmography to measure plasma levels of IL-6, nitrate, nitrite and c-GMP. In the treatment group, calf blood flow increased significantly from 3.01 (2.56 to 3.3) ml min(-1) 100 mL(-1) of tissue before garlic to 3.46 (3.0 to 4.03) ml min(-1) 100 mL(-1) of tissue after 7 days of garlic (P = 0.001). Plasma IL-6 concentrations increased significantly from 54.6 (32.3 to 151.6) mcg/mL before to 151 (135.75 to 422.3) mcg/mL after 7 days of garlic (P = 0.02). However, there was no significant change in the plasma levels of nitrate, nitrite and c-GMP after the garlic (P = 0.4, 0.9 and 0.65 respectively). In the control group, resting calf blood flow and plasma levels of IL-6, nitrite, nitrate and c-GMP remained unchanged after 7 days (P = 0.62, 0.92, 0.28 and 0.35 respectively). Calf blood flow showed a non-linear correlation with plasma IL-6 levels after garlic supplementation (r = 0.86, p = <0.001) but not before. There was no significant relationship between blood flow and plasma nitrate, nitrite and c-GMP in either groups and between blood flow and IL-6 in the control group. These data suggest that garlic supplementation increases resting tissue blood flow and this may be mediated by IL-6.

Adult↗
PubMed2004

Can lymphatic drainage be measured non-invasively in human limbs, using plethysmography?

There is always rapid volume restitution of the accumulated interstitial fluid after a VCP (venous congestion plethysmography) protocol. It has been suggested that backward extrapolation of the relationship between applied hydrostatic pressure and fluid filtration may give a measure of tissue J (vL) (lymph flow); if so, this could be of immense value in pathophysiological investigations. We hypothesized that the congestion pressure decrease following the VCP protocol might be the stimulus for activating the observed rapid interstitial fluid removal mechanism. We investigated this hypothesis by using a cumulative small step VCP protocol to a maximum arterial diastolic pressure, followed by a mirror image of step pressure decreases. The increases and decreases in cuff pressure produced capillary filtration capacities that were not significantly different from one another [(3.8+/-1.0) x 10(-3) and (3.7+/-1.2) x 10(-3) ml x 100 ml(-1) x min(-1) x mmHg(-1) respectively]. However, we did observe a significant 3-fold increase in estimated lymph flow between the up and 'mirror' down protocol. Moreover, the calculated supine control value, reflecting interstitial fluid removal ( J (vL)), of 0.03+/-0.03 ml x 100 ml(-1) x min(-1) was within the range of lymph flows in human limbs described by other workers, as was the 3-fold increase to 0.09+/-0.03 ml x 100 ml(-1) x min(-1) following the release of the venous congestion. These results support the notion that strain-gauge plethysmography might provide a non-invasive means of assessing peripheral lymph flow in human limbs.

Adult↗
PubMed2003

Microvascular permeability is related to circulating levels of tumour necrosis factor-alpha in pre-eclampsia.

INTRODUCTION: The mechanism for the increased microvascular permeability which, underline many of the complications of pre-eclampsia, remain unexplained. It has been suggested that a factor present in the maternal circulation in pregnancies complicated by the disease may be responsible for increased microvascular permeability. In this study, we have investigated the relationship between filtration capacity (K(f)), an index of microvascular permeability, and maternal levels of VEGF, leptin and TNF-alpha, all of which are known permeability factors whose plasma levels are increased in pre-eclampsia. METHODS: We used a small cumulative pressure step venous congestion plethysmography protocol to compare K(f), an index of microvascular permeability, during the third trimester of 20 women with pre-eclampsia, 18 normal pregnant women and 18 non-pregnant female matched controls. Blood samples were obtained to measure plasma levels of VEGF, leptin, TNF-alpha plasma protein concentrations and full blood count. RESULTS: Microvascular filtration capacity (K(f)) was significantly increased in pre-eclampsia compared to the other groups (P<<0.0001, ANOVA). K(f) was also increased in the normal pregnant group when compared to the non-pregnant controls (P=0.02). Plasma levels of VEGF, leptin and TNF-alpha were significantly greater in pre-eclampsia compared to normal pregnancy and non-pregnant controls (P<0.0001, ANOVA, for all three analyses). Total plasma protein and albumin concentrations were significantly lower in the normal pregnant and pre-eclamptic groups, compared to the non-pregnant controls (P<0.0001, ANOVA). K(f) was significantly related to TNF-alpha in pre-eclampsia (r=0.53, P=0.018), and with VEGF in the non-pregnant controls (r=0.6, P=0.02). No significant relationship was observed between K(f) and VEGF, leptin and TNF-alpha during normal pregnancy. There was a significant inverse correlation between plasma albumin concentration and filtration capacity in the normal pregnant (r=-0.94, P<0.0001) and non-pregnant (r=-0.87, P<0.0001) groups but not in the women with pre-eclampsia (r=-0.18, P=0.8). CONCLUSIONS: These data show that that microvascular filtration capacity is significantly increased in pre-eclampsia, and correlates with circulating levels of TNF-alpha but not leptin or VEGF.

Adult↗
PubMed2001

Differential association of CD45 isoforms with CD4 and CD8 regulates the actions of specific pools of p56lck tyrosine kinase in T cell antigen receptor signal transduction.

An investigation into the role of CD45 isoforms in T cell antigen receptor signal transduction was carried out by transfecting CD45-negative CD4(+)CD8(+) HPB-ALL T cells with the CD45R0, CD45RBC, and CD45RABC isoforms. Fluorescence resonance energy transfer analysis showed that the CD45R0 isoform, but not the CD45RBC or CD45RABC isoforms, was found as homodimers and also preferentially associated with CD4 and CD8 at the cell-surface. A comparison was therefore made of T cell antigen receptor signaling between sub-clones expressing either CD45R0 or CD45RBC. Under basal conditions CD4-associated p56(lck) tyrosine kinase activity and cellular protein tyrosine phosphorylation levels were higher in the CD45R0(+) than in the CD45RBC(+) sub-clones. Upon CD3-CD4 ligation, TCR-zeta phosphorylation, ZAP-70 recruitment to the p21/p23 TCR-zeta phosphoisomers, ZAP-70 phosphorylation, as well as p56(lck), c-Cbl and Slp-76 phosphorylation, were all markedly increased in CD45R0(+) compared with CD45RBC(+) cells. T cell antigen receptor (TCR) stimulation alone also promoted c-Cbl phosphorylation in CD45R0(+) but not in CD45RBC(+) cells. Our results are consistent with a model in which association of CD45R0 with CD4 generates a more active pool of CD4-associated p56(lck) kinase molecules. Upon CD3-CD4 co-ligation, the active p56(lck) increases the intensity of T cell antigen receptor signal transduction coupling by promoting TCR-zeta chain phosphorylation and ZAP-70 recruitment.

CD4 Antigens↗