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Biomedical subjects

F Valone

Publications and source records attributed to F Valone.

8 recordsLinked to original sources

Rapid debulking and CD34 enrichment of filgrastim-mobilized peripheral blood stem cells by semiautomated density gradient centrifugation in a closed system.

Filgrastim-mobilized peripheral blood progenitor cells (PBPC) are used for hematopoietic reconstitution after myeloablative therapy for malignancies, but the large number of cells collected in a single apheresis frequently presents a problem for storage or further processing. We have evaluated the use of CD34 Buoyant Density Solution-PBPC, an ultralight-density colloidal silica suspension, for debulking and enrichment of CD34+ cells in PBPC preparations in a semiautomated system. Cells were collected from four filgrastim-treated normal donors using the COBE Spectra. The separation procedure was carried out with Plasma-Lyte A and DNase 5 U/ml using the COBE 2991. Following processing and washing, there was a 26% recovery of nucleated cells, 2.6-fold enrichment of CD34+ cells, 68% recovery of CD34+ cells, 88% recovery of CFU-GM, 73% recovery of BFU-E, 1 log depletion of CD3+ cells, 0.5 log depletion of CD56+ cells, and 1 log depletion of CD19+ cells. These results were not significantly different from those obtained when PBPC were separated over CD34 Buoyant Density Solution-PBPC by centrifugation in tubes. Using CD34 Buoyant Density Solution-PBPC, mononuclear preparations of PBPC can be enriched rapidly for CD34+ cells and depleted of lymphocytes in a semiautomated closed system using reagents produced according to good manufacturing practice (GMP).

Antigens, CD34

Hepatic cancers and their response to chemoembolization therapy. Quantitative image-guided 31P magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: Hepatic embolization combined with intra-arterial administration of cytostatic drugs (chemoembolization) is frequently used to treat primary and metastatic cancers to the liver. Quantitative phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to assess the metabolic state of hepatic cancers and their metabolic response to chemoembolization. METHODS: Fifteen localized 31P MRS studies were performed on five patients with liver tumors. Thirteen healthy volunteers served as controls. Metabolite ratios and molar metabolite concentrations were calculated. RESULTS: Untreated hepatic tumors, relative to normal controls, showed elevated phosphomonoester/adenosine triphosphate (PME/ATP) ratios, reduced concentrations of ATP and inorganic phosphate (Pi), and normal phosphodiester (PDE) concentrations. As an acute response to chemoembolization, ATP, PME, and/or PDE concentrations diminished, whereas Pi concentrations increased or stayed relatively constant. Long-term follow-up after chemoembolization showed decreased PME/ATP and increased ATP concentrations in the absence of changes on standard magnetic resonance and computed tomographic images. CONCLUSIONS: These preliminary spectroscopic data suggest that quantitative 31P MRS can be successfully used to monitor directly metabolic response to hepatic chemoembolization.

Adenocarcinoma

P-31 spectroscopy study of response of superficial human tumors to therapy.

Studies were performed to characterize phosphorus-31 magnetic resonance (MR) spectra obtained from 10 superficial human tumors outside the brain and to determine whether P-31 MR spectroscopy could allow detection of a response to therapy before a change in tumor size was measured. The ratio of phosphomonoester to adenosine triphosphate peak intensities (PME/ATP) was unusually large in all tumors studied. The average PME/ATP in lymphomas (1.8 +/- 0.5) was greater than in nonlymphoma cancers (1.1 +/- 0.15). The average PME/ATP for all tumors studied (1.4 +/- 0.5) was much greater than that of underlying skeletal muscle (0.23 +/- .09). Eight of the tumors were studied before and after therapy. Responders were distinguished from nonresponders on the basis of changes in tumor size. PME/ATP decreased during therapy in three lymphomas that responded to therapy. In an adenocarcinoma and Ewing sarcoma that did not respond to therapy, PME/ATP increased. PME/ATP remained constant in two squamous cell carcinomas that responded to therapy and decreased in one squamous cell carcinoma that decreased in size by 40% but was classified as a nonresponder. Changes in PME/ATP did not always parallel changes in tumor size during therapy. In two patients, a decrease in PME/ATP preceded a decrease in tumor size. In four patients, PME/ATP increased transiently during periods when tumor size remained constant.

Adenosine Triphosphate

Interaction of platelet-activating factor with interferon-gamma in the stimulation of interleukin-1 production by human monocytes.

Platelet-activating factor (PAF) produces both early and late inflammatory responses in vivo. The late and persistent responses to PAF may result from the production of cytokines, such as interleukin-1 (IL-1). The effects of PAF on IL-1 release by human monocytes were studied with PAF alone and in combination with interferon-gamma. These studies involved the use of D10.G4.1 cells in a proliferation assay to determine the actual concentration of active IL-1 in monocyte supernatant and pellet fractions. These studies confirmed that PAF stimulates IL-1 release at two different ranges of PAF concentrations, 100 fM to 1 pM and 100 pM to 1 nM. PAF inhibited IL-1 release at 1 or 10 pM. PAF effects on IL-1 release were specific to the form of PAF that is biologically active in most system; (S)-PAF and lyso-PAF had no effect. When monocytes were incubated with both PAF and interferon-gamma, IL-1 release was greatly stimulated at the same two ranges of PAF concentrations, 100 fM to 1 pM and 100 pM to 1 nM of PAF. PAF and interferon-gamma interacted synergistically to enhance significantly the release of IL-1.

Adult

Response of tumors to therapy studied by 31P magnetic resonance spectroscopy.

Magnetic resonance (MR) methods have been used to study the metabolic and vascular response of model tumors to tumor necrosis factor (TNF). Magnetic resonance measurements demonstrated acute reductions in tumor blood flow, measured from tumor uptake of D2O, and in tumor adenosine triphosphate (ATP), measured by 31P magnetic resonance spectroscopy (MRS) following administration of TNF. The decrease in ATP generally followed reduction in tumor blood flow, and therefore was probably due to ischemia caused by damage to tumor vasculature. Superficial human tumors have been studied by MRS to characterize their 31P spectra, and to measure metabolic changes during therapy. The ratio of the intensities of the phosphomonoester (PME) and ATP resonances (PME/ATP) was much higher in tumors than in the normal tissue displaced by the tumors. During therapy, decreases in PME/ATP were detected that paralleled, but did not anticipate, decreases in tumor size. In some cases, a transient increase in PME/ATP was detected during therapy, which did not correlate with changes in tumor size, and which may reflect stimulation of cell growth in some tumor zones.

Adenosine Triphosphate

Doxorubicin in pregnancy: possible transplacental passage.

Two pregnant women with lymphoproliferative disorders were treated with doxorubicin-containing regimens. Both patients delivered shortly after a dose of doxorubicin. One child was healthy and the other was stillborn. Measurements of anthracycline levels in placental, cord, and fetal tissues by high-performance liquid chromatography suggest that doxorubicin may be transported across the placenta.

Adult