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Biomedical subjects

L Walker

Publications and source records attributed to L Walker.

At least 199 records · Page 11Linked to original sources

Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.

Carcinoma, Transitional Cell↗

Milrinone in heart failure. Acute effects on left ventricular systolic function and myocardial metabolism.

Milrinone, a new bipyridine compound related to amrinone, is a potent non-adrenergic inotrope in experimental preparations and also shows vasodilator activity. In the present study the haemodynamic and metabolic effects of milrinone were evaluated in 12 patients with congestive heart failure. Milrinone 5 mg given orally produced a sharp reduction in left ventricular end diastolic pressure without significantly affecting stroke volume. The improvement in left ventricular function was due to a combination of vasodilation and positive inotropism. Thus small reductions in blood pressure and systemic vascular resistance were associated with increments in the isovolumic indices of left ventricular function. The relation between left ventricular end systolic pressure and dimension was displaced leftwards and downwards. Only reductions in left ventricular cavity dimension were statistically significant, however. Though myocardial oxygen consumption did not change significantly, it tended to increase whereas lactate consumption tended to decrease. This trend towards oxygen imbalance suggests the need for caution in the use of milrinone in patients with severe coronary artery disease.

Adult↗

Adolescent dialysands in group therapy.

Adolescents are particularly vulnerable to the psychological effects of chronic illness and its treatment. Group treatment of girls with renal failure proved to be of therapeutic value in improving self-image and reducing emotional stress.

Adolescent↗

Medical information via CD-ROM technology.

Because of the volume of traditional bibliographic medical literature there is an obvious need for improved retrieval techniques. The Micromedex Computerized Clinical Information System provides end user friendly retrieval plus critically evaluated referenced information offering the user the opportunity to obtain answers to specific medical questions.

Drug Information Services↗

Autocrine models of B-lymphocyte growth. I. Role of cell contact and soluble factors in T-independent B-cell responses.

The requirements for triggering human B cells to DNA synthesis by T-independent polyclonal activators were examined. Optimal S phase entry of purified resting B cells infected with Epstein-Barr virus (EBV) or confronted with killed particles of Staphylococcus aureus Cowan Strain I (SAC) required a high density of cells in culture. Experiments varying culture vessel geometry and culture volumes revealed that the initial limiting quantity was a soluble activity generated in the B-cell cultures. A parallel observation was noted in the requirements for the sustained growth of EBV-transformed lymphoblasts. Autostimulatory soluble factors harvested from such cultures were able to augment DNA synthesis in low density cultures of resting cells triggered by EBV or SAC. Below a critical cell number, however, soluble factors by themselves, were not sufficient either for supporting primary B-cell responses or for maintaining the proliferation of transformed lymphoblasts. By employing conditions which encouraged cell contact it was found that a second, non-harvestable factor requiring cell proximity for its action was also necessary to promote B-cell growth. The implications of these findings for autocrine and paracrine models of B-cell activation are discussed.

B-Lymphocytes↗

The use of cytocentrifuge preparations for the demonstration of T cell surface antigens.

Cytocentrifuged cell preparations have been evaluated as substrates for the demonstration by immunofluorescence of T cell surface antigens. Results obtained by a 2-stage method with fluorescent conjugate specific for the isotype of the first stage monoclonal antibody, and by a 3-stage procedure employing an intermediate antiserum to mouse IgG as amplifying agent, showed good correlation with those obtained by a standard technique performed on cells in suspension. These methods have the advantages of requiring fewer cells and less antibody and the cytocentrifuge preparations may be stored for batch assay.

Animals↗

Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Immobilized rabbit and rat C-reactive protein (CRP) were found to selectively bind apolipoprotein B (apoB)-containing lipoproteins (low density lipoprotein, LDL and very low density lipoprotein, VLDL) from whole serum in a manner similar to that previously reported with human CRP. In acute phase human serum the CRP is in a free form, not complexed with lipoprotein or any other macromolecular ligand, and in acute phase serum from most rabbits fed on a normal diet the rabbit CRP was also free. However, in acute phase serum or heparinized plasma from hypercholesterolemic rabbits part or all of the CRP was found by gel filtration and immunoelectrophoretic techniques to be complexed with beta-VLDL, an abnormal apoB-containing plasma lipoprotein present in these animals. The presence of extent in different serum samples of CRP complexed with lipoprotein correlated closely with the serum apoB concentration. The formation of complexes between native, unaggregated rabbit CRP in solution and apoB-containing lipoproteins was readily demonstrable experimentally both with the isolated proteins and in whole serum. In all cases these interactions were calcium-dependent and inhibitable by free phosphoryl choline. The present findings extend earlier work in man and the rabbit and indicate that among the C-reactive proteins from different species, which are structurally highly conserved, the capacity for selective binding to apoB-containing plasma lipoproteins is also a constant feature. These interactions may therefore be related to the in vivo function of CRP in all species and this function may in turn be relevant to pathological conditions, such as atherosclerosis, in which lipoproteins are important.

Animals↗

Potential value of oral beta 2-adrenoceptor agonists in congestive heart failure: a haemodynamic and metabolic study.

This study was designed to investigate and compare the haemodynamic and metabolic responses to pirbuterol and salbutamol in patients with congestive heart failure and coronary artery disease. Attention was directed towards the effects these beta 2-adrenoceptor agonists have on left ventricular systolic function, systemic and coronary haemodynamics and myocardial substrate metabolism. Sixteen patients were randomly allocated to treatment with either pirbuterol 20 mg or salbutamol 6 mg. Since no statistically significant differences between the responses to these drugs were observed, combined data for both agents are presented. Ninety minutes after the drug intervention cardiac index increased from 2.2 +/- 0.1 to 2.9 +/- 0.2 1/min per m2 (P less than 0.001) in association with marked reductions in systemic vascular resistance (from 22 +/- 1 to 15 +/- 1 units, P less than 0.001) and increments in left ventricular dp/dtmax (from 1074 +/- 85 to 1422 +/- 133 mm Hg/sec, P less than 0.05). Modest reductions in left ventricular end-diastolic pressure (from 21 +/- 1 to 15 +/- 1 mm Hg, P less than 0.01) were observed. Heart rate increased from 82 +/- 5 to 91 +/- 4 beats/min (P less than 0.01) but the small fall in mean arterial pressure (from 86 +/- 3 to 78 +/- 3 mm Hg) was not significant. Drug-induced coronary vasodilatation reduced coronary coronary vascular resistance from 0.65 +/- 0.06 to 0.47 +/- 0.04 units (P less than 0.01) and led to a marked increase in coronary sinus blood flow (from 124 +/- 9 to 155 +/- 9 ml/min, P less than 0.05). Arterial levels of free fatty acids increased from 0.78 +/- 0.13 to 1.05 +/- 0.18 mmol/l (P less than 0.05) resulting in the preferential utilization of this substrate as a myocardial energy source. Despite the substantial haemodynamic improvement, however, no significant increase in myocardial oxygen uptake or lactate production was observed. Thus, in patients with coronary artery disease and congestive heart failure pirbuterol and salbutamol improve left ventricular function by a combination of afterload reduction and positive inotropism such that no appreciable deterioration in myocardial energetics occurs.

Adult↗

T-cell proliferation and expression of MHC class II antigens.

Two monoclonal antibodies to major histocompatibility complex (MHC) class II antigens, which in combination identify beta chains encoded by the SB and DR loci, were used to investigate which of these gene products were expressed at the cell surface of unstimulated T cells and at various stages of mitogen-induced T-cell maturation. In tests on blood lymphocytes from healthy donors 12% of T cells expressed class II antigens, but only SB antigens were expressed. During activation of T lymphocytes, SB-coded antigens were expressed before DR antigens, and the kinetics of SB expression correlated with the proliferative response of T cells. These results and consideration of recent reports from other laboratories lead us to suggest that SB-coded class II antigens play a role in T-cell proliferation.

Cells, Cultured↗

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.

Adult↗