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Biomedical subjects

J Doll

Publications and source records attributed to J Doll.

At least 55 records · Page 3Linked to original sources

Treatment planning for conformation therapy using a multi-leaf collimator.

In high energy photon therapy an optimum dose distribution is achieved with an irradiation from several directions, thus adapting the field shape to the target volume. Some methods of irradiation planning using these techniques are presented. The result of such a treatment planning is demonstrated.

Humans↗

Biochemical regulation of adenylate cyclase in murine melanoma clones with different metastatic properties.

The regulation of adenylate cyclase in murine melanoma tumor cell clones with different metastatic capacities has been studied in intact cells and isolated membrane preparations. Analysis of the responses of intact cells from a number of B16 melanoma clones revealed that treatment with melanocyte-stimulating hormone (MSH) or the diterpene, forskolin, produced significantly greater accumulation of intracellular cyclic adenosine 3',5' monophosphate (cAMP) in strongly metastatic clones than in weakly metastatic tumor cell clones. In contrast, in isolated membranes from the same panel of clones, the extent of activation by forskolin but not by MSH correlated with metastatic capacity. Sodium fluoride and 5'-guanyl-beta-gamma-imidodiphosphate [Gpp(NH)p] also stimulated adenylate cyclase in isolated membranes but the extent of activation did not correlate with the metastatic behavior of the donor cells. A combination of forskolin and Gpp(NH)p proved to be a sensitive prospective indicator for identifying differences in the metastatic capabilities of individual B16 melanoma clones. Adenylate cyclase in membrane preparations from strongly metastatic B16 clones displayed synergistic activation but stimulation of the enzyme from weakly metastatic clones was less than additive. To test the generality of these findings, similar investigations were performed on B16-BL6 melanoma cells, a highly invasive subline of the B16 melanoma, and the K1735, an ultraviolet-light-induced murine melanoma arising in a different mouse strain (C3H). Consistent with their high metastatic potential, clones derived from the B16-BL6 melanoma displayed elevated levels of hormonally-stimulated adenylate cyclase, thereby confirming, for this tumor system, a close association between hormonal responsiveness and metastatic capacity. In contrast, K1735 melanoma cell clones exhibited significant interclonal variation in adenylate cyclase activity and metastatic performance, but no consistent relationship between the two traits was detected. Differences in the regulation and/or the intrinsic catalytic capacity of adenylate cyclase may account, at least in part, for the variation in hormonal responsiveness observed among B16 clones with distinct metastatic properties and suggest that cAMP-dependent molecular processes may be required for the expression of B16 melanoma experimental metastatic potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenylyl Cyclases↗

Pharmacokinetics of ranitidine in acute upper gastrointestinal haemorrhage.

A pharmacokinetic study of ranitidine was performed in 14 patients with haematemesis divided into two groups according to the severity of blood loss. Pharmacokinetic values were calculated from plasma concentrations after the first of three daily injections (100 mg) and compared with those obtained in five healthy volunteers (50 mg i.v.). There were no significant differences between patients in the two haemorrhage groups and controls. The low, or even questionable, effectiveness of histamine H2-receptor antagonists in the treatment of upper gastrointestinal haemorrhage does not seem to be due to pharmacokinetic factors.

Acute Disease↗

[Improvement of the non-invasive diagnosis of coronary heart disease using a new double-isotope method for the noninvasive determination of coronary transit times].

In conventional myocardial Thallium-201 scintigraphy, regional myocardial Thallium-201 activity is compared to the area of normal, i.e., maximal activity. In the presence of multivessel coronary artery disease, this mode of evaluation may yield false negative results. -In 87 patients suffering from coronary artery disease and in 26 controls, after simultaneous i.v. injection of Thallium-201 and Technetium-99m coronary transit times of Thallium-201 were determined as the interval between arrival of the tracer in the aortic root and the onset of its extraction in different myocardial areas. - Patients with hemodynamically significant coronary artery stenoses (greater than or equal to 75%) revealed a significant increase in coronary transit times over septum, apex, or posterolateral wall of the left ventricle. Using maximal coronary transit times, i.e., the largest of the regional values, an excellent discrimination between patients with severe coronary artery stenoses and controls was achieved. Following coronary vasodilatation with dipyridamole, even subcritical (50-75%) coronary artery stenoses could be detected with high sensitivity, since the shortening of coronary transit times in patients with subcritical stenoses was less pronounced as compared to controls. - Especially in the presence of diffuse three-vessel coronary artery disease, the quantitative assessment of regional coronary transit times yields important parametric data in addition to those obtained by conventional Thallium-201 scintigraphy combining static imaging with rapid sequence analysis of time-activity curves.

Coronary Disease↗

[Autochthonous Plasmodium falciparum malaria and the malarial liver].

When P. falciparum malaria is diagnosed in France in a patient who has not travelled to an endemic area, transmission by blood transfusion or direct contact with an infected person, and indigenous malaria should be considered. With reference to the observation reported in this paper, the manifestations of malarial hepatitis are recalled and their diagnostic significance is discussed. In P. falciparum malaria, malarial hepatitis indicates the development of a complete cycle including the pre-erythrocytic phase; this is strongly in support of indigenous malaria, and against malaria following blood transfusion or direct contact in which there is no pre-erythrocytic phase.

Adult↗

Processing of 201T1 serial images for the assessment of myocardial clearance and redistribution.

Regional activity changes over the myocardium after IV injection of 201T1 were assessed in 90 patients by applying a superposition algorithm for paired images. The kinetics were expressed as quotients C1/C2 of the initial divided by the delayed count rate within any myocardial segment. Regarding the total left ventricular myocardium, normal subjects showed count rate ratios (C30 min/C4 h) of 1.75 +/- 0.075 (SD, n = 19) when the nuclide was injected under submaximal (80% of maximum) exercise. In patients with triple-vessel disease (n=21) the corresponding values were 1.46 +/- 0.05, in single-vessel (n=14) disease the quotients averaged 1.62 +/- 0.12. Average quotients in poststenotic myocardial segments increased from 1.46 before to 1.73 following bypass surgery in cases of graft patency (n=8), while a decrease was observed in a patient with occlusion of the bypass graft. In small-vessel disease and in congestive cardiomyopathy, global values of 1.50 +/- 0.07 (n=7) and 1.53 +/- 0.12 (n=19) were obtained. The display of C1/C2 matrices provided typical patterns in uptake defects caused by ischemic heart disease and by congestive cardiomyopathy. The procedure described may provide diagnostic information in addition to conventional myocardial scintigraphy in triple-vessel disease, in patients with angina who fail to demonstrate hemodynamically significant coronary artery stenoses, and in patients with inhomogeneous T1-scintigrams.

Coronary Disease↗

Evolution of tumor cell heterogeneity during progressive growth of individual lung metastases.

The metastatic properties of tumor cell clones isolated from individual lesions of B16 melanoma metastatic to lung have been examined at different stages in the evolution of metastasis. Clonal analysis of metastatic lesions produced by B16 melanoma populations containing clones with identifiable, stable drug-resistance markers revealed that the majority (greater than 80%) of experimental metastases produced by intravenous injection of tumor cells are of unicellular origin. During the early stages of their growth (less than 25 days after initial tumor cell arrest), the majority of metastatic lesions contain cells with indistinguishable metastatic phenotypes (intralesional clonal homogeneity) although different clonally homogeneous lesions from the same host contain tumor cells with different metastatic phenotypes (interlesional clonal heterogeneity). Progressive growth of metastatic lesions is accompanied by emergence, within originally clonally homogeneous lesions, of variant tumor cells with altered metastatic properties (intralesional clonal heterogeneity). By 40-45 days after initial arrest of injected tumor cells in the lung, 90% of the metastatic lesions are populated by cells with heterogeneous metastatic phenotypes.

Animals↗

Comparison of the metastatic properties of B16 melanoma clones isolated from cultured cell lines, subcutaneous tumors, and individual lung metastases.

Tumors produced by s.c. injection of uncloned B16 melanoma cell lines contain clonal tumor cell subpopulations with widely differing metastatic properties, including clones that are nonmetastatic. Similar metastatic heterogeneity exists in clones isolated from the same cell lines cultured in vitro. In B16 melanoma sublines (B16-BL6, B16-BV8, and B16-BP8) selected for enhanced invasive and metastatic behavior, the proportion of clones with high metastatic capacity is increased relative to the parent cell line. The cellular composition of metastases produced by s.c. or i.v. injection of the uncloned parent cell line has also been examined. Some metastases are populated by clones with indistinguishable metastatic properties (intralesional clonal homogeneity) while others yield clones with different metastatic properties (intralesional clonal heterogeneity). The range of clonal diversity in heterogeneous metastases is, however, substantially less than in the parent line. The number of metastases yielding clones with heterogeneous metastatic phenotypes is higher for "spontaneous" metastases arising from s.c. tumors than in "experimental" metastases produced by i.v. injection of single-cell suspensions. Studies using B16 cells bearing specific biochemical markers indicate that clonally homogeneous metastases are of monoclonal origin and that metastases populated by clones with heterogeneous metastatic phenotypes are of polyclonal origin.

Animals↗

Interactions among clonal subpopulations affect stability of the metastatic phenotype in polyclonal populations of B16 melanoma cells.

Analysis of the metastatic properties of clones isolated from mouse B16 melanoma cell lines (B16-F1 and F10) shows extensive cellular heterogeneity and the presence of subpopulations that have widely differing metastatic abilities. This pattern of metastatic heterogeneity is maintained during serial passage in vitro and in vivo. In contrast, even a short serial passage of individual clones isolated from these heterogeneous parent lines results in rapid emergence of variant subclones that have different metastatic properties. If several clones are mixed and cocultivated, this instability is not expressed. These data suggest that, in polyclonal populations, the various clonal subpopulations somehow interact with one another to "stabilize" their relative proportions within the population. Restriction of clonal diversity by selective killing of the majority of clones in a polyclonal population eliminates the stabilizing restraints and stimulates rapid emergence of new subpopulations to create heterogeneous populations containing a new panel of phenotypically diverse subpopulations that then reach stable proportions until the next selection pressure(s) is encountered.

Animals↗

[Role of Clostridium and its toxin in pseudo-membranous colitis (author's transl)].

At present many authors consider that pseudo-membranous colitis is of bacterial origin. The main pathogenic agent is Clostridium difficile. It is not easy to isolate this organism in the stool, selective media are under study. It liberates a lipo-glycoprotein exotoxin during lysis. It is only partially purified, its structure is not fully elucidated. Its molecular weight is not yet precisely determined. It consists of several polymerised polypeptide fragments of molecular weight 50 000. It is a thermolabile acid and alkaline sensitive cytotoxin which acts on the cell membranes and the ileo-caeco-colonic mucosa of man and animals. Clostridium difficile is transmissible by a small number of high risk carrier subjects who are potentially patients with pseudo-membranous colitis. Antibiotic therapy may lead to unbalance of the ecosystem represented by the bacterial flora of the digestive tract and favour the multiplication of a resistant strain to the administered antibiotic. The appearance of pseudo-membranous colitis requires the association of sufficient bacterial development (equal or greater than 10(7) germs per gram of stools) and the liberation of a cytotoxin. The pathogenic treatment consists of antibiotic therapy by Vancomycin or Metronidazole which seems, at present, the most active on the germs and a toxin absorbent, such as Cholestyramine, Coliptol hydrochloride or Heavy metals.

Animals↗

[Discriminant analysis in the quantitative evaluation of lung scintigrams (author's transl)].

Lung scintigrams made with 99mTc-MAA in a group of patients and a control group were compared and classified by a discriminant analysis based on two regional methods and several parameters for quantitative characterisation of the regions. Improved results are gained by a regional division of the lung orientated in the pulmonary lobes and segments and by combining several parameters.

Analysis of Variance↗

In vitro selection of murine B16 melanoma variants with enhanced tissue-invasive properties.

New assay methods have been devised to quantitate tumor cell invasion of tissues of differing histological complexity maintained as organ cultures in vitro (chorioallantoic membrane of chicken, mouse urinary bladder, and canine blood vessel. In addition to quantitating tumor cell invasion, these methods also allow recovery of invasive cells for comparison with noninvasive cells. These methods have been used to select variant sublines from murine B16-F1 and B16-F10 melanoma lines that display significantly greater tissue-invasive abilities than the parent lines. B16 variant sublines selected in vitro for increased invasiveness through the bladder wall or vein also show a significant increase in their ability to form spontaneous and experimental metastases in vivo. In contrast, cells from the same parent cell line selected for increased invasiveness through the chorioallantoic membrane do not show significant alterations in metastatic behavior. We conclude that invasive variants can be isolated from the parent B16 tumor by several in vitro methods and that the level of expression of the invasive phenotype in vivo may be determined by the severity of the selection procedure in vitro.

Amnion↗