Biomedical subjects
Publications and source records attributed to G R Sutherland.
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CD26 is a lymphocyte cell surface antigen which is increased during T-cell activation and is also expressed in other tissues. It is an atypical serine protease belonging to the prolyl oligopeptidase family. CD26 has been implicated in a variety of biological functions including T-cell activation, cell-to-cell adhesion, and recently in HIV infection. This paper describes, through the isolation and partial sequencing of eight human CD26 genomic clones, the first information on the genomic organization of the prolyl oligopeptidase family. We have established that the human CD26 gene spans approximately 70 kilobases (kb) and contains 26 exons, ranging in size from 45 base pairs (bp) to 1.4 kb. The nucleotides that encode the serine recognition site (G-W-S-Y-G) are split between two exons. This clearly distinguishes the genomic organization of the prolyl oligopeptidase family from that of the classical serine protease family. The 5' flanking domain of the CD26 gene contains neither a TATA box nor a CAAT box, but a 300 bp region extremely rich in C and G (72%) contains potential binding sites for several transcriptional factors. The human CD26 gene encodes two messages sized at about 4.2 and 2.8 kb. These are both expressed at high levels in the placenta and kidney and at moderate levels in the lung and liver. Only the 4.2 kb mRNA was expressed at low levels in skeletal muscle, heart, brain, and pancreas. Fluorescence in situ hybridization on metaphase chromosome spreads located the human CD26 gene to the long arm of chromosome 2(2q24.3).
An investigation has been carried out on the velocity resolution, spatial resolution and accuracy of Doppler images as part of a study into the Doppler display of cardiac tissue motion. Test-phantoms were designed to perform this work and images were captured on a computer. The characteristics of the phantom images and of the image capture process were studied. The smallest spatial detail that was observed in the Doppler image was 3 mm by 3 mm. Doppler receive gain and Doppler ensemble size both affected velocity resolution. Different target materials gave different measures for velocity resolution. This could be related to the different back-scatter intensities of the materials.
The cyclic variation of ultrasonic integrated backscatter from the left ventricular posterior wall and interventricular septum of the heart is now well documented in the literature, with minimal values occurring at end-systole and maximal at end-diastole. However, little work has been performed to date to determine whether cyclic cardiac variation of other, more easily derived, backscatter parameters exists. In this study, 20 baseline, epicardial, long-axis cardiac-cycle sequences were obtained from eight open-chest pigs, yielding a total of 285 ultrasonic frames of RF data, which were analysed off-line on a Sun workstation. In addition, the video data from these studies was digitised and collected from each scan. Five backscatter parameters, calculated in the time-domain, including (1) the average integrated backscatter; (2) the average of the backscatter power from the log-compressed data; (3) the square of the average of the uncompressed radio frequency (RF) amplitude; (4) the square of the average of the RF amplitude from the log-compressed data; and (5) the square of the average grey-scale video data, were analysed and their variation throughout the cardiac cycle correlated against that obtained from integrated backscatter measurements. The backscatter values obtained were referenced to a gel calibration phantom widely used for 2-D calibration studies. Significant (p < 0.001), good correlation existed between the four backscatter parameters derived from the RF data. Reduced correlation was obtained between the video backscatter parameter and those derived from the RF data. Maximum cyclic variation between systole and diastole was measured from the integrated backscatter parameter and minimum from the three log-compressed data sets.
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Four examples of discordance between karyotypes prepared from direct and PHA-stimulated neonatal blood samples are presented. The specimens were initially studied by direct methods to establish a neonatal karyotype rapidly. The patients are described and the significance of the findings is discussed.
Transoesophageal echocardiography (TOE) was performed during closed chest cardiopulmonary resuscitation (CPR) in 18 subjects in cardiac arrest. Compression of all four cardiac chambers resulted in forward flow in the pulmonary and systemic circulations, retrograde pulmonary vein flow and incomplete mitral valve closure. Antegrade pulmonary vein flow and left ventricular filling occurred exclusively during the relaxation phase. These findings support the cardiac pump theory of CPR and are incompatible with the thoracic pump mechanism. TOE merits further investigation as a device to monitor and guide resuscitation efforts during CPR.
Using a scanner whose colour Doppler mode has been adapted to display tissue motion (instead of blood flow), velocity gradients have been detected across the myocardium. A velocity gradient is a gradual spatial change in the value of velocity estimates. Velocity gradients have potential for assessing regional myocardial contractility. 28 M-mode scans were performed on nine normal volunteers at different locations in the left-ventricle posterior wall. In each case simultaneous Doppler M-mode and pulse-echo M-mode images were obtained. Doppler velocity gradient (DVG) was calculated from Doppler M-mode images and rate of change of wall thickness (RCWT) was calculated from pulse-echo M-mode images. In all Doppler M-mode images statistically significant velocity gradients were observed. In all but one scan, cyclically consistent peaks in DVG occur relative to the electrocardiogram waveform. 99% of systolic and 89% of early diastolic peaks in RCWT have a corresponding peak in DVG. Velocity gradients are consistent with wall thickness changes, suggesting that they have potential for assessment of myocardial contractility.
The pentavalent antimonial sodium stibogluconate is the mainstay of anti-leishmanial therapy. Sodium stibogluconate is less cardiotoxic than antimony and the trivalent derivatives, but has been associated with dose-related electrocardiographic changes. The effect of the currently-used regimen of sodium stibogluconate (20 mg/kg/day for 20 days) on cardiac function is uncertain. We studied 12 soldiers, mean age 24 years, with proven cutaneous leishmaniasis treated with this regimen. There were no significant changes in echocardiographic indices of left ventricular systolic or diastolic function during treatment. Indices of myocardial electrical stability (heart-rate variability and episodes of overt supraventricular and ventricular arrhythmias) were unchanged, but there was a reversible decrease in T-wave amplitude during treatment. Systolic and diastolic blood pressure fell and the heart rate increased during treatment. This regimen of sodium stibogluconate does not measurably impair left ventricular systolic or diastolic function. Minor T-wave changes occur during treatment, but there is no increase in arrhythmia frequency or change in heart-rate variability. In most young fit patients, this regimen has no cardiac side-effects. However, idiosyncratic reactions cannot be excluded, and patients with malnutrition, impaired renal function or pre-existing heart disease may be more sensitive to any cardiotoxic properties of sodium stibogluconate.
BACKGROUND: Transesophageal echocardiography with transversal planes offers many advantages in the evaluation of patients with congenital anomalies of atrium, allowing visualization of obscure areas, not visualized with traditional echocardiography, as appendages, venous connections, upper interatrial defects. The aim of this paper is to check what advantages the transesophageal imaging in longitudinal plane, recently insert in biplane probes, might confer over transversal plane imaging in the evaluation of patients with congenital heart disease of atrium and venous connections. METHODS: We carried out a prospective study on 70 patients (49 adults and 22 children) with congenital heart diseases of this area. Fifty-six studies out of 71 were preoperative diagnostic, 15 were carried out in the late postoperative period. Twenty-two studies were performed under general anaesthesia during concomitant cardiac catheterisation, 49 were carried out in outpatient clinic. All the transesophageal diagnoses were subsequently confirmed at either catheterization or surgery. Lesions studied included 36 atrial septal defects (ASD) ostium secundum, 6 interatrial septal aneurysms, 1 ASD coronary sinus, 5 ASD venous sinus, 5 partial and 2 complete atrioventricular septal defects, 1 double outlet right ventricle; in operated patients 2 ASD ostium secundum, 2 ASD sinus venosus, 11 post Mustard or Senning in TGA. RESULTS: Anomalies either better defined or that obtained important additional informations by long axis scanning (vs transverse scanning) included: ASD ostium secundum 36/36, ASD multiple 1/3, caval obstruction in Mustard or Senning 4/5, anterior mitral valve cleft 2/5, left superior vena cava to coronary sinus 3/3. Features visualized by longitudinal plane alone were: ASD coronary sinus 1/1, caval obstruction in sinus venosus operated 1/1, multiple ASD 2/3, coronary artery fistula to right atrium 1/1; for associated features anterior bringing leaflets 2/2, left ventricular outflow tract obstruction 2/2, right ventricular outflow tract obstruction 1/1. Anomalies better characterized by transversal plane versus longitudinal plane were: ASD ostium primum 2/7, ASD sinus venosus sinus 3/5; for associated anomalies VSD inlet 1/1. Features visualized by transversal plane alone were: right upper pulmonary vein in superior vena cava 4/4, right upper pulmonary vein to right atrium 1/1, DIA ostium primum 5/7, ASD sinus venosus 2/5, superior vena cava obstruction in Mustard 1/5, left juxtaposition of the atrial appendages 1/1. The transversal plane alone provided the correct morphologic and hemodynamic diagnosis in 74/88 (84%) (in this group longitudinal plane gave 68% additional informations), the longitudinal planes in 69/88 (78%). However in 11% of cases longitudinal plane was the only means for identifying the congenital lesion and transversal plane in 16%. It was the combination of longitudinal and transverse scanning which gave in 97% the correct complete morphologic diagnosis. CONCLUSIONS: Thus we conclude that both planes are required for optimal transesophageal evaluation of congenital disease of atrium and venous connection.
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CD30 is a surface marker for neoplastic cells of Hodgkin's lymphoma and shows sequence homology to members of the tumor necrosis factor (TNF) receptor superfamily. Using a chimeric probe consisting of the extracellular domain of CD30 fused to truncated immunoglobulin heavy chains, we expression cloned the cDNA cognate from the murine T cell clone 7B9. The encoded protein is a 239 amino acid type II membrane protein whose C-terminal domain shows significant homology to TNF alpha, TNF beta, and the CD40L. Cross-hybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proliferation of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones. The human and murine genes map to 9q33 and the proximal region of chromosome 4, respectively.
The receptors for interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are heterodimers comprised of ligand specific alpha chains and a common beta chain. The genes encoding the IL-5 receptor alpha chain and the common beta chain reside on chromosome 3 and 22 respectively, while the GM-CSF receptor alpha chain gene (CSF2RA) has been mapped to the pseudoautosomal region (PAR) of the sex chromosomes, which is a 2.6-Mb stretch of homologous sequence at the tips of the short arms within which a single obligatory recombination occurs during male meiosis. We have mapped the gene encoding the IL-3 receptor alpha chain (IL3RA) to the sex chromosomes by polymerase chain reaction (PCR) analysis of human-mouse or human-chinese hamster cell hybrids, and to Yp13.3 and Xp22.3 using fluorescence in situ hybridization. To explore the possibility that IL3RA is located within the pseudoautosomal region we screened the Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees for an informative-restriction fragment-length polymorphism (RFLP) that showed male meiotic recombination. Two informative CEPH pedigrees were identified that displayed this phenomenon, confirming the psuedoautosomal location of IL3RA. Using long-range restriction mapping we have found that IL3RA maps to the same 190-kb restriction fragment as CSF2RA, suggesting that a cytokine receptor gene cluster may reside in the PAR.
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