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Biomedical subjects

C E Thomas

Publications and source records attributed to C E Thomas.

124 records · Page 7Linked to original sources

Postoperative depression of tumour-directed cell-mediated immunity in patients with malignant disease.

Leucocytes from 46 melanoma patients, 45 breast carcinoma patients, and 95 control donors were tested by the leucocyte migration test against the supernatants of homogenates of malignant melanomas, breast carcinomas, simple breast tumours, and breasts showing simple cystic disease. By comparison with controls inhibition of migration occurred significantly more frequently when tumour patients' leucocytes were exposed to extracts of histogenetically similar tumours.Cell-mediated immunity to tumour-associated antigens was measured in 12 patients with breast carcinoma and 12 with malignant melanoma immediately before surgical operation and in the postoperative period. All patients tested before operation showed significant inhibition of migration on contact with extracts of histogenetically similar tumours. Postoperatively the degree of leucocyte migration inhibition was reduced in all patients with melanoma and breast carcinoma. Significant inhibition of leucocyte migration returned in most patients 6-22 days after operation.

Antigens, Neoplasm↗

Data-driven analysis approach for biomarker discovery using molecular-profiling technologies.

High-throughput molecular-profiling technologies provide rapid, efficient and systematic approaches to search for biomarkers. Supervised learning algorithms are naturally suited to analyse a large amount of data generated using these technologies in biomarker discovery efforts. The study demonstrates with two examples a data-driven analysis approach to analysis of large complicated datasets collected in high-throughput technologies in the context of biomarker discovery. The approach consists of two analytic steps: an initial unsupervised analysis to obtain accurate knowledge about sample clustering, followed by a second supervised analysis to identify a small set of putative biomarkers for further experimental characterization. By comparing the most widely applied clustering algorithms using a leukaemia DNA microarray dataset, it was established that principal component analysis-assisted projections of samples from a high-dimensional molecular feature space into a few low dimensional subspaces provides a more effective and accurate way to explore visually and identify data structures that confirm intended experimental effects based on expected group membership. A supervised analysis method, shrunken centroid algorithm, was chosen to take knowledge of sample clustering gained or confirmed by the first step of the analysis to identify a small set of molecules as candidate biomarkers for further experimentation. The approach was applied to two molecular-profiling studies. In the first study, PCA-assisted analysis of DNA microarray data revealed that discrete data structures exist in rat liver gene expression and correlated with blood clinical chemistry and liver pathological damage in response to a chemical toxicant diethylhexylphthalate, a peroxisome-proliferator-activator receptor agonist. Sixteen genes were then identified by shrunken centroid algorithm as the best candidate biomarkers for liver damage. Functional annotations of these genes revealed roles in acute phase response, lipid and fatty acid metabolism and they are functionally relevant to the observed toxicities. In the second study, 26 urine ions identified from a GC/MS spectrum, two of which were glucose fragment ions included as positive controls, showed robust changes with the development of diabetes in Zucker diabetic fatty rats. Further experiments are needed to define their chemical identities and establish functional relevancy to disease development.

Algorithms↗

Three-dimensional quantitative analysis of hemispheric asymmetry in the human superior temporal region.

The recent observations of overall symmetry of the caudal infrasylvian region by Steinmetz et al. (1990) and Witelson and Kigar (1991, 1992) diverge from earlier findings of leftward asymmetry in this region (Geschwind and Levitsky, 1968; Galaburda et al., 1987; Larsen et al., 1989). To address this inconsistency, we measured the entire infrasylvian surface posterior to Heschl's gyrus from coronal magnetic resonance images of 10 young, normal, right-handed subjects. Computer models were constructed by tracing contours of this region and then interpolating a 3D triangle mesh between each pair of adjacent contours. Measurements of these models showed no significant directional asymmetry. The same contour set was used to obtain measurements with a conventional algorithm that does not interpolate a surface between contours. The results obtained with the second method showed significant leftward asymmetry. These results suggest that in some cases, unbalanced distortions due to folding differences of the hemispheres are sufficient to obtain spurious findings of left-right asymmetry. This supports the claim of Steinmetz and Witelson that leftward asymmetry is restricted to the temporal bank of the caudal infrasylvian surface, and is balanced by rightward asymmetry of the parietal bank.

Adolescent↗

Glomerular and renal hemodynamics during converting enzyme inhibition (SQ20,881) in the dog.

It has been suggested that intrarenal levels of angiotensin II may preferentially control efferent arteriolar resistance or may influence the glomerular filtration coefficient (Kf). To examine these possibilities, micropuncture and clearance experiments were performed on nine anesthetized dogs evaluating renal and glomerular hemodynamics before and during the administration of an angiotensin converting enzyme inhibitor (SQ20,881). During the micropuncture measurements, renal arterial pressure was reduced to range of 85 to 90 mm Hg in order to maximize renin secretion and intrarenal formation of angiotensin II. Also, this procedure minimizes potential errors in the determination of single nephron glomerular filtration rate (SNGFR) and of glomerular pressure when estimated by techniques that require complete blockade of proximal tubule fluid flow. During the administration of SQ20,881, a converting enzyme inhibitor (CEI), renal blood flow increased significantly by 13%, but GFR was not altered. There were no significant alterations in SNGFR, proximal tubule pressure, peritubular capillary pressure or estimated glomerular pressure. By using the micropressure measurements in combination with the whole kidney hemodynamic data, it was estimated that afferent resistance was reduced 23%. Although significant decreases in efferent resistance could not be documented, there was a tendency for this variable to decrease also. Neither Kf nor effective filtration pressure were altered significantly by CEI. These results do not support the contention that intrarenal effects of angiotensin II are exerted predominantly on the efferent arteriolar resistance segments; rather, they suggest that angiotensin may exert a modest tonic effect on both pre- and postglomerular resistance elements in the anesthetized hydropenic dog.

Angiotensin II↗

Influence of converting enzyme inhibition on renal hemodynamics and glomerular dynamics in sodium-restricted dogs.

Clearance and micropuncture experiments were performed to evaluate the influence of converting enzyme inhibition (CEI) (SQ 14,225) on renal hemodynamics, glomerular filtration rate (GFR), segmental vascular resistances, and superficial nephron function in anesthetized sodium restricted dogs. In one series (n = 8), renal blood flow (RBF) and GFR exhibited a high degree of autoregulatory efficiency when renal arterial pressure (RAP) was reduced from 126 +/- 5 to 86 +/- 1 mm Hg. With RAP maintained at the reduced level, CEI elicited increases in RBF (3.9 +/- 0.3 to 5.8 +/- 0.5 ml/min per g kw) and GFR (0.81 +/- 0.03 to 0.94 +/- 0.04 ml/min per g kw). With return of RAP to spontaneous levels during continued CEI, RBF and GFR autoregulatory efficiency was maintained, and was similar to that observed in control dogs subjected to the same procedures (n = 5). In the micropuncture experiments (n = 12), RAP was maintained at the reduced level (87.5 +/- .9 mm Hg), and measurements were made before and during CEI. Proximal tubule pressure, peritubular capillary pressure, stop flow pressure, and single nephron GFR (SNGFR) increased significantly. Regression analysis suggested that the increases in SNGFR were associated with small increases in the filtration coefficient. CEI reduced preglomerular resistance by 29% to 35% and efferent arteriolar resistance by 24% to 32%. These results indicate that the increased activity of the renin-angiotensin system that occurs during salt restriction exerts approximately equivalent vasoconstrictor influences on both preglomerular and postglomerular vascular resistance elements.

Animals↗

[Effect of polymyxin B on the hemolytic mechanism of the genus Listeria].

The contact between polymyxin B and human blood cells produced a double effect on the haemolytic activity of Listeria monocytogenes, L. seeligeri and L. ivanovii hemolysins. At low polymyxin B concentrations the antibiotic promoted erythrocyte lysis whereas at higher antibiotic levels, hemolysis inhibition was observed. According to the effects of polymyxin B, hemolytic profiles were established for each hemolysin. L. monocytogenes and L. seeligeri exhibited a similar profile with maximum hemolytic activity at 1000 U/ml polymyxin B. L. ivanovii displayed a different profile, with two maximum hemolytic activities: one similar to that showed by L. monocytogenes and L. seeligeri at 1000 U/ml, and another peak of hemolysis at 4000 U/ml polymyxin B.

Bacterial Toxins↗