Biomedical subjects

Andrew J Morgan

Publications and source records attributed to Andrew J Morgan.

8 recordsLinked to original sources

PubMed2006

Non-invasive vascular impedance measures demonstrate ocular vasoconstriction during isometric exercise.

AIMS: The calculation of impedance for a vascular network is a common method used in circulation studies. Impedance indices (the ratios of the harmonics of pressure to the harmonics of flow) provide the investigator with a measure of the opposition to blood flow in a pulsatile system and are a proven indicator for vasculopathy. Previous studies investigating the eye's opposition to blood flow have concentrated on simple measures of resistance (the ratio of mean pressure difference to mean flow) which are more appropriate to a steady state or non-pulsatile system. The purpose of this study is to demonstrate a new, non-invasive, method to determine the vascular impedance of the eye during the known physiologic stress of sustained isometric exercise. METHODS: Waveforms of ocular blood flow and carotid arterial blood pressure were measured non-invasively. Ocular blood flow waveforms were calculated using the Langham-Silver method by measuring the small fluctuations in intraocular pressure intraocular pressure over time with a high fidelity pneumatonometer. Carotid arterial blood pressure waveforms were determined using a SphygmoCor electronic tonometer held over the common carotid artery of the neck. Both waveforms were recorded simultaneously in normal volunteers under two conditions: (1) a baseline resting state and (2) during sustained isometric exercise. The components of the two waveforms (the harmonics) were calculated using a Fast Fourier transform and expressed as a ratio in order to determine a set of impedance values for each condition. The first four impedance values were calculated. RESULTS: 12 volunteers (six male: six female) with a mean age of 27 years (range 22-32 years) were recruited to the study. In comparison to baseline resting conditions, mean carotid blood pressure and heart rate both increased significantly during exercise: baseline mean carotid blood pressure, 82.6+/-8.2 mm Hg vs exercise mean carotid blood pressure, 93.8+/-12.8 mm Hg (p<0.001); baseline pulse rate, 64.6+/-9.1 BP(m) vs exercise pulse rate, 71.8+/-9.7 BP(m) (p<0.001). Compared to resting conditions, the first and third impedance values demonstrated significant change during exercise: the first impedance value rose (83.9+/-25.6 mm Hg-s/microl to 117.1 +/- 40.9 mm Hg-s/microl, p = 0.01) and the third impedance value fell (487.9 +/- 294.7 mm Hg-s/microl to 248.3+/-206.8 mm Hg-s/microl, p = 0.01). CONCLUSIONS: The present study demonstrates, for the first time, a practical non-invasive method of calculating an index of impedance moduli for the pulsatile quotient of blood flow to the eye. Furthermore, during controlled isometric exercise, the impedance moduli displayed changes consistent with that known for a vascular system during vasoconstriction. The calculation of impedance moduli for the eye therefore shows promise for future investigations into ocular conditions where vascular obstruction is an aetiological factor.

Adult↗

PubMed2004

Use of gHgL for attachment of Epstein-Barr virus to epithelial cells compromises infection.

Epstein-Barr virus (EBV) is a lymphotropic herpesvirus. However, access to B lymphocytes during primary infection may be facilitated by replication in mucosal epithelial cells. Attachment and penetration of EBV into these two cell types are fundamentally different. Both the distribution of receptors and the cellular origin of the virus impact the efficiency of infection. Epithelial cells potentially offer a wide range of receptors with which virus can interact. We report here on analyses of epithelial cells expressing different combinations of receptors. We find that the stoichiometry of the virus glycoprotein complex that includes gHgL and gp42 affects the use of gHgL not just for entry into epithelial cells but also for attachment. Penetration can be mediated efficiently with either a coreceptor for gp42 or gHgL, but the use of gHgL for attachment as well as penetration greatly compromises its ability to mediate entry.

Cell Line, Tumor↗

PubMed2003

Regional variability in visual field sensitivity during hypercapnia.

PURPOSE: Previous investigations have demonstrated a relative vascular autoregulatory inefficiency of the inferior compared to the superior retina in healthy subjects breathing increased CO(2). The purpose of this study was to determine whether the superior and inferior visual field sensitivities of healthy eyes are similarly affected during mild hypercapnia. DESIGN: Experimental study. METHODS: Visual field analysis (Humphrey Field Analyser; SITA standard 24-2 program) was carried out on one randomly selected eye of 22 subjects (mean age, 27.7 +/- 5 years) during normal room air breathing and isoxic hypercapnia. The Student paired t-tests were used to compare the visual field indices mean deviation (MD) and pattern standard deviation (PSD) for each breathing condition. A secondary, sectoral analysis of mean pointwise sensitivity was performed for each condition. In each case a P value of <.01 was considered statistically significant (Bonferroni corrected). RESULTS: Visual field MD was -0.23 +/- 0.95dB during room air breathing and -0.49 +/- 1.04dB during hypercapnia (P =.034). Sectoral pointwise mean sensitivity deteriorated by 0.46dB (P =.006) in the upper visual hemifield during hypercapnia, whereas no significant difference was observed for the lower hemifield (P =.331). CONCLUSIONS: The upper visual hemifield exhibited a significantly greater degree of deterioration in pointwise visual field mean sensitivity compared to the lower hemifield during hypercapnic conditions. This suggests that the upper visual hemifield and hence inferior retina is more susceptible to insult during hypercapnia than the superior retina in healthy individuals. A regional susceptibility of inferior retinal function to altered vascular or metabolic effects may account for the earlier and more frequent inferior nerve fibre damage associated with glaucomatous optic neuropathy.

Adult↗

PubMed2003

The B subunit of Escherichia coli heat-labile enterotoxin enhances CD8+ cytotoxic-T-lymphocyte killing of Epstein-Barr virus-infected cell lines.

Epstein-Barr virus (EBV) is associated with a number of important human cancers, including nasopharyngeal carcinoma, gastric carcinoma, and Hodgkin's lymphoma. These tumors express a viral nuclear antigen, EBV nuclear antigen 1 (EBNA1), which cannot be presented to T cells in a major histocompatibility complex class I context, and the viral latent membrane proteins (LMPs). Although the LMPs are expressed in these tumors, no effective immune response is made. We report here that exposure to the cholera-like enterotoxin B subunit (EtxB) in EBV-infected lymphoblastoid cell lines (LCLs) enhances their susceptibility to killing by LMP-specific CD8(+) cytotoxic T lymphocytes (CTLs) in a HLA class I-restricted manner. CTL killing of LCLs is dramatically increased through both transporter-associated protein-dependent and -independent epitopes after EtxB treatment. The use of mutant B subunits revealed that the enhanced susceptibility of LCLs to CTL killing is dependent on the B subunit's interaction with GM(1) but not its signaling properties. These important findings could underpin the development of novel approaches to treating EBV-associated malignancies and may offer a general approach to increasing the presentation of other tumor and viral antigens.

Amino Acid Sequence↗

PubMed2002

Spectral content of the intraocular pressure pulse wave: glaucoma patients versus normal subjects.

BACKGROUND: Many studies have found that the intraocular pressure (IOP) is lower in glaucomatous populations than in normal groups. An alternative method of analysis, commonly used in the investigation of arterial blood pressure, is to reduce the pulse waveform to its component Fourier parts. The purpose of this study, therefore, was to determine whether such a technique is applicable to the IOP pulse and to investigate whether it was superior at differentiating diseased from healthy eyes. METHODS: Using a pneumatonometer, continuous 10-s IOP recordings were taken from 10 glaucoma patients and 10 normal subjects. The IOP recordings were then analysed using the fast Fourier transform (FFT) to determine their spectral components. In addition, standard IOP parameters (pulse amplitude, pulse volume, and pulsatile ocular blood flow) were measured to allow comparison with the waveform analysis technique. RESULTS: Analysis by FFT successfully determined the IOP pulse's higher spectral components up to the fourth harmonic. In addition, although standard measurements of the IOP pulse (such as pulse amplitude) were insignificant, the second ( P=0.034), third ( P=0.015) and fourth ( P=0.013) harmonics of the waveform successfully differentiated between the glaucoma and normal groups. CONCLUSION: Spectral analysis of the IOP pulse appears to be a promising technique in the investigation of ocular vascular disease.

Blood Pressure↗

PubMed2002

The effect of corneal thickness and corneal curvature on pneumatonometer measurements.

PURPOSE: The purpose of this study was to investigate the influence of corneal topography and thickness on intraocular pressure (IOP) and pulse amplitude (PA) as measured using the Ocular Blood Flow Analyzer (OBFA) pneumatonometer (Paradigm Medical Industries, Utah, USA). METHODS: 47 university students volunteered for this cross-sectional study: mean age 20.4 yrs, range 18 to 28 yrs; 23 male, 24 female. Only the measurements from the right eye of each participant were used. Central corneal thickness and mean corneal radius were measured using Scheimpflug biometry and corneal topographic imaging respectively. IOP and PA measurements were made with the OBFA pneumatonometer. Axial length was measured using A-scan ultrasound, due to its known correlation with these corneal parameters. Stepwise multiple regression analysis was used to identify those components that contributed significant variance to the independent variables of IOP and PA. RESULTS: The mean IOP and PA measurements were 13.1 (SD 3.3) mmHg and 3.0 (SD 1.2) mmHg respectively. IOP measurements made with the OBFA pneumatonometer correlated significantly with central corneal thickness (r = +0.374, p = 0.010), such that a 10 microm change in CCT was equivalent to a 0.30 mmHg change in measured IOP. PA measurements correlated significantly with axial length (part correlate = -0.651, p < 0.001) and mean corneal radius (part correlate = +0.459, p < 0.001) but not corneal thickness. CONCLUSIONS: IOP measurements taken with the OBFA pneumatonometer are correlated with corneal thickness, but not axial length or corneal curvature. Conversely, PA measurements are unaffected by corneal thickness, but correlated with axial length and corneal radius. These parameters should be taken into consideration when interpreting IOP and PA measurements made with the OBFA pneumatonometer.

Adolescent↗

PubMed2002

Clinical evaluation of the dynamic observing tonometer.

PURPOSE: The Dynamic Observing Tonometer (SmartLens, Ophthalmic Development Company AG, Zürich, Switzerland) is a diagnostic contact lens that allows continuous measurement of intraocular pressure, in addition to providing the investigator with a view of the posterior pole and anterior chamber angle. The purpose of this study was to determine the accuracy of this tonometer and the repeatability of the intraocular pressure measurements. PATIENTS AND METHODS: The intraocular pressure was measured by Goldmann applanation tonometry in one randomly chosen eye of 40 subjects (median age 66 years, range 21-77 years). The intraocular pressure, pulse amplitude and 10-second continuous tonometric recordings were then taken using the Dynamic Observing Tonometer and a pneumatonometer. Accuracy was determined by calculating the mean bias and 95% limits of agreement of measurements made with the Dynamic Observing Tonometer against measurements made with the Goldmann and pneumatonometer. Repeatability was evaluated by calculating the differences between pairs of repeated measurements against the mean value and by calculating reliability coefficients. RESULTS: Intraocular pressure measurements made with the Dynamic Observing Tonometer had a mean bias of +2.1 mm Hg (95% limits of agreement: -4.0 to +8.2 mm Hg) compared with Goldmann tonometry. There was a reasonable correlation between Goldmann and Dynamic Observing Tonometer intraocular pressure readings (r = 0.78, P < 0.01). In measuring pulse amplitude, the Dynamic Observing Tonometer was found to have a mean bias of +0.4 mm Hg (95% limits of agreement: -1.6 to +2.3 mm Hg) compared with the pneumatonometer (r = 0.78, P < 0.01). In assessing the repeatability of intraocular pressure measurements, the first Dynamic Observing Tonometer reading was on average 0.4 mm Hg higher than the second (95% limits of agreement: -3.8 to +4.6 mm Hg) with a coefficient of reliability of 0.91. For pulse amplitude readings, the first reading was on average 0.1 mm Hg lower than the second (95% limits of agreement: -1.4 to +1.2 mm Hg) with a coefficient of reliability of 0.90. CONCLUSION: Intraocular pressure measurements taken with the Dynamic Observing Tonometer had a small positive bias compared with Goldmann tonometry. The pulse amplitude values correlated well with those obtained with a pneumatonometer and the repeatability of intraocular pressure measurements was similar to that found in other commercially available tonometers.

Adult↗

PubMed2002

Primary immune responses by cord blood CD4(+) T cells and NK cells inhibit Epstein-Barr virus B-cell transformation in vitro.

Epstein-Barr virus (EBV) transformation of B cells from fetal cord blood in vitro varies depending on the individual sample. When a single preparation of EBV was simultaneously used to transform fetal cord blood samples from six different individuals, the virus transformation titer varied from less than zero to 10(5.9). We show that this variation in EBV transformation is associated with a marked primary immune response in cord blood samples predominately involving CD4(+) T cells and CD16(+) CD56(+) NK cells. After virus challenge both CD4(+) T cells and NK cells in fetal cord blood cultures expressed the lymphocyte activation marker CD69. The cytotoxic response against autologous EBV-infected lymphoblastoid cell line (LCL) targets correlated with the number of CD16(+) CD69(+) cells and was inversely correlated with the virus transformation titer. Although NK activity was detected in fresh cord blood and increased following activation by the virus, killing of autologous LCLs was detected only following activation by exposure to the virus. Both activated CD4(+) T cells and CD16(+) NK cells were independently able to kill autologous LCLs. Both interleukin-2 and gamma interferon were produced by CD4(+) T cells after virus challenge. The titer of EBV was lower when purified B cells were used than when whole cord blood was used. Addition of monocytes restored the virus titer, while addition of resting T cells or EBV-activated CD4(+) T-cell blasts reduced the virus titer. We conclude that there are primary NK-cell and Th1-type CD4(+) T-cell responses to EBV in fetal cord blood that limit the expansion of EBV-infected cells and in some cases eliminate virus infection in vitro.

Antigens, CD↗