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E R Bacon

Publications and source records attributed to E R Bacon.

28 records · Page 2Linked to original sources
PubMed1994

Time-lapse quantitative computed tomography lymphography: assessing lymphatic function in vivo.

RATIONALE AND OBJECTIVES: Immobility and massage produce different local limb lymph flow rates. We studied their influence on accumulation of radiopaque nanoparticulates in regional lymph nodes of normal rabbits. METHODS: Quantitative lymphography at 10-min intervals was used to follow the transport of subcutaneous (s.c.) nanoparticulates produced from insoluble esters of diatrizoic acid. In one design, both hindpaws received 0.5 ml of nanoparticulate s.c., and one hindpaw was massaged. In a second design, one hindpaw was injected and massaged while imaging the popliteal, presacral, and paraaortic nodes every 10 min. RESULTS: Gentle massage rapidly increased popliteal node accumulation in comparison with the immobile limb. On the massaged side, mean Hounsfield (HU) units, maximum Hounsfield units, and calculated iodine were significantly greater at 10 min and all subsequent times. In the node transfer experiments, it took 12, 30, and 45 min, respectively, to obtain 100-HU mean attenuation; 200-HU maximum attenuation thresholds were achieved at 20, 47, and 69 min, respectively. CONCLUSION: Quantitative computed tomography lymphography reflects local lymph physiology. Gentle massage of the s.c. injection site is a powerful lymphotropic stimulus.

Analysis of Variance↗
PubMed1994

Nanoparticulate computed tomography contrast agents for blood pool and liver-spleen imaging.

RATIONALE AND OBJECTIVES: We investigated the properties of a group of iodine-containing, insoluble compounds formulated as nanoparticles for use as potential blood pool and liver-spleen contrast agents. METHODS: High-resolution, quantitative computed tomography (CT) was performed prior to and at intervals following the intravenous administration of the contrast agents to rabbits. Time-density characteristics for three organs were evaluated. RESULTS: Excellent enhancement of blood (< or = 232 Hounsfield units [HU]), liver (< or = 263 HU), and spleen (< or = 350 HU) was achieved at the administered dose of 3.0 ml/kg. The composition of the agents influenced the biodistribution, as well as the residence time in blood, and time to peak enhancement in liver. CONCLUSION: Iodinated nanoparticulate compounds are promising CT contrast agents. Development of agents with desirable pharmacokinetic and biodistribution profiles may permit application-specific contrast enhancement.

Animals↗
PubMed1994

Pharmacologic and pharmacodynamic effects of the selective low Km cyclic AMP phosphodiesterase III inhibitors WIN 63291 and WIN 62582.

We describe the biochemical, pharmacologic, and in vivo pharmacodynamic profiles of two novel inhibitors of the cyclic GMP-inhibitable, low Km cyclic AMP phosphodiesterase (PDE) III; WIN 63291, a 6-quinolinyl analogue of the prototypic PDE III inhibitor milrinone and WIN 62582, an imidazopyridinone. Both WIN 62582 and WIN 63291 competitively inhibit PDE III from rat, dog, and human heart and from rat and canine aorta with IC50 values of 5-37 and 55-80 nM, respectively; the IC50 values for milrinone ranged from 300 to 520 nM. WIN 62582 and WIN 63291 are at least 1,000-fold selective for PDE III relative to inhibition of PDE isozymes I, II, IV, and V. We evaluated WIN 62582 and WIN 63291 in conscious rats and dogs after intravenous (i.v.) and oral (p.o.) administration. The dose of WIN 62582 required to reduce mean arterial blood pressure (MAP) by 20% (ED20) in rats was 1.8 mg/kg, with a pharmacodynamic duration of action of approximately 2 h. In comparison, the estimated i.v. ED20 for WIN 63291 in rats was 0.4 mg/kg, with a pharmacodynamic duration of action > 6 h. In conscious dogs, the i.v. doses of WIN 62582 and 63291 required to increase left ventricular (LV)dP/dtmax significantly were 0.1 and 0.01 mg/kg, respectively. In dogs, WIN 63291 0.1 mg/kg p.o. increased LVdP/dtmax by 86% in 30 min; LVdP/dtmax remained increased by 60% for at least 6 h. In comparison, WIN 62582, 0.3 mg/kg p.o., increased LVdP/dt by 56% in 30 min and remained increased by 40% at 6 h.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

3-Quinolinecarboxamides. A series of novel orally-active antiherpetic agents.

A series of novel 3-quinolinecarboxamides that are structurally similar to the quinolone class of antibacterial agents possess excellent antiherpetic properties. By modifying the quinoline ring at the 1-, 2-, 3-, and 7-positions, analogues were identified that have up to 5-fold increased HSV-2 plaque-reduction potency relative to acyclovir. In a single-dose mouse model of infection, one of the most potent derivatives in vitro, 1-(4-fluorophenyl)-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarbo xamide (97), displayed comparable oral antiherpetic efficacy to acyclovir at 1/16 the dose; in a multiple-dose regimen, however, 97 was 2-fold less potent. In mice dosed orally with 97, sustained plasma drug levels were evident that may account for the high efficacy observed. The molecular mechanism of action of these agents is not known; however, based on in vitro studies with acyclovir resistant mutants, it is likely that the mechanism differs from that of acyclovir. In vitro plaque-reduction potency was not generally predictive of oral efficacy in mice. An X-ray crystal structure of 97 corroborated the assignment of structure and provided useful insights as to the effect of conformation on plaque-reduction potency.

Acyclovir↗
PubMed1987

Identification and characterization of a differentiation-specific antigen on normal and malignant murine erythroid cells.

Rauscher murine erythroleukemia cells grow continuously in vitro and undergo terminal differentiation in response to the physiological inducer erythropoietin. In the course of this developmental process they express many erythroid-specific markers. In order to investigate the expression of cell surface determinants during Rauscher cell differentiation we generated monoclonal antibodies to uninduced cells. Using an anti-Rauscher cell monoclonal antibody, we have identified a cell surface determinant, designated ERY-1, that is present on normal murine erythroid cells. This determinant is apparently absent from the early progenitor BFU-E, but is present on the more mature progenitors CFU-E and CFC-E. It disappears during erythroid maturation and is absent from the mature erythrocyte. This pattern of ERY-1 expression is exhibited with remarkable fidelity during the erythropoietin-induced differentiation of Rauscher cells. Such differentiation-specific expression of the ERY-1 determinant suggests that it may play a functional role in erythropoiesis.

Animals↗
PubMed1985

T-cell regulation of erythropoiesis during acute lymphoblastic leukemia.

How and where erythropoiesis is maintained during advanced leukemic disease is an important and, as yet, unresolved question in hematology. To address the potential role of T-lymphocytes as cells that regulate CFU-E differentiation during leukemogenesis, an experimental model of disease has been developed in inbred Balb/c mice. Specifically, three-week-old Balb/c By mice were injected with murine sarcoma virus-murine leukemia virus-Moloney (MSV-MuLV-M), which resulted 6-8 months later in the development of immunoblastic T-cell sarcomas with a leukemic phase. Splenic T cells from either normal or tumor-bearing mice were assessed for their relative ability to modulate erythroid differentiation. Quantitatively, T cells, Ly1 or Ly 2,3 T-cell subsets isolated from tumor-bearing animals significantly enhanced erythropoiesis when compared with comparable normal T-cell subsets. These data suggest that the compensatory shift of erythropoiesis from the bone marrow to the spleen observed during leukemogenesis was facilitated by splenic T cells. In this circumstance, the enhanced erythropoietic function may be mediated by splenic T cells, which are selectively activated by virus.

Animals↗
PubMed1984

Regulation of B cell lymphomagenesis by a malignant Qal+ inducer T cell clone.

A series of Thy-1.2+ Ly-1+ Qa-1+ malignant T cell clones have been isolated from murine sarcoma virus-murine leukemia-Moloney (MSV-MuLV-M)-induced B cell lymphomas or from MSV-MuLV-M-infected B6 mice. These T cell clones enhance both antigen-independent and -dependent lymphocyte differentiation and function. They also induce the differentiation of granulocytes and erythrocytes in the stem cell compartment, a function that parallels the immunopathology of the disease in vivo. The malignant T cell appears to sustain B lymphoma growth in vivo by releasing a factor (BCGF) that promotes B cell proliferation.

Animals↗
PubMed1983

Amplification of granulopoiesis by T cell subpopulations.

Regulation of granulopoiesis by activated splenic T lymphocyte subpopulations was investigated. The addition of syngeneic T cells activated by the mitogen concanavalin A or by mixed lymphocyte response (MLR) to normal bone marrow cultures stimulated granulopoiesis, while, in contrast, resting T cells did not. Functional analyses of Fluorescence Activated Cell Sorter (FACS) purified subpopulations of MLR activated T cells showed that both subsets enhanced granulocyte colony forming cells (CFUc) differentiation. Further studies using Ly 23+ T cells stimulated in vitro to suppress the primary generation of plaque forming cells (PFC) showed that these "suppressor cells" simultaneously enhanced CFUc differentiation. These results show that T cell "helper" function in hematopoietic regulation is not restricted to the inducer subset of T cells.

Animals↗