to effect their critical functions. Certain myeloid growth factors, including G-CSF, inhibit random migration of neutrophils in vitro and theoretically may alter neutrophil G-CSF administration to normal donors results in granulocyte apheresis yields generally greater than those migration to these sites in vivo. 11 To assess the distribution of G-CSF-mobilized neutrophils in vivo, LA products col-observed with other neutrophil mobilizing agents. In vitro, neutrophils cultured with G-CSF exhibit pro-lected from normal donors receiving G-CSF were labeled with indium-111 and infused into neutropenic allogeneic longed survival; however, the random migration of neutrophils exposed to this agent is inhibited. Although BMT recipients. Serial scintigraphic images were obtained post-infusion. Results of this pilot study of five patients transfused neutrophils mobilized with agents other than G-CSF migrate to sites of inflammation or infection in support the hypothesis that G-CSF-mobilized neutrophil products retain their ability to localize to sites of inflam-vivo, this has yet to be demonstrated with infusion of G-CSF-mobilized neutrophils into neutropenic human mation in vivo. subjects. Five neutropenic allogeneic bone marrow transplant (BMT) patients each received a fresh infusion of G-CSF-mobilized indium-labeled irradiated Methods white blood cells (WBC) apheresed from HLA-matched normal donors on day +5 post-transplant. Localization In all cases, the donor of the granulocyte apheresis products was also the donor of the bone marrow product for each of activity on delayed scintigraphic images of indiumlabeled WBC scans to sites of tissue damage recipient. The protocol was approved by the Institutional Review Board and accrued five donor/recipient pairs. Eligi-(oral/nasopharynx in two patients with mucositis and terminal ileum/cecum in one with diarrhea) occurred, bility criteria for donors included age у15 and р70 years, WBC у4000/l, ANC у1500/l, platelet count and supports the hypothesis that G-CSF-mobilized HLA-matched donor neutrophils which have been у100 000/l, hematocrit (Hct) у30%. All donors were HLA-A, B, DR six antigen serologic matched and ABO irradiated are functional after infusion into neutropenic recipients. compatible with the recipients. Otherwise, donors satisfied standard blood donation criteria as determined by the Food Keywords: granulocyte transfusions; G-CSF; indium labeled and Drug Administration (FDA) and as interpreted by the Blood Bank Director. Recipients between the ages of 15 and 55 years undergoing related donor allogeneic BMT for malignant disease were eligible. Alloimmunization, as G-CSF is a safe and effective agent for mobilization of defined by unresponsiveness to platelet transfusions, 12 was neutrophils in normal donors, consistently resulting in cell not evident in the study recipients. Antileukocyte antibodies yields of 4-10 × 10 10 per leukapheresis (LA) procedure 1,2 were not measured. Informed consent for entry of recipients as opposed to Ͻ3 × 10 10 cells/LA procedure with ot...
Hepatic extraction, cellular and subcellular localization of gelatin stabilized Tc-99m sulfur colloid was studied in the rat model with time sequenced microautoradiography from 15 min to 24 h following I.V. administration of the tracer. Hepatic lobular and cellular distribution, quality and quantity of focal grain pattern, grain clusters, remained essentially constant for the period of study. Grain clusters were associated predominantly with Kupffer cells lining the peripheral segment of hepatic lobular sinusoids. Subcellular localization of gelatinized Tc sulfur colloid, stained prior to the I.V. administration with osmium tetroxide, was demonstrated with a transmission electron microscope in unosmicated liver tissue. Extracted Tc sulfur colloid particles were attached in groups to cytoplasmatic membranous intrasinusoidal projections of activated Kupffer cells. Intracytoplasmatic phagocytosis was not demonstrated. The kinetic arrest and en groupe extraction of Tc sulfur colloid particles at the Kupffer cell membrane suggests a specific membrane receptor site and specific Tc sulfur colloid particle-plasma protein interaction at the time of extraction. Hepatic extraction of gelatinized Tc sulfur colloid thus reflects primarily extra and intra hepatic hemodynamics and does not serve as an indicator of phagocytic hepatic reticuloendothelial system function.
Lipid soluble agents which chelate radioactive cations have several potential uses in nuclear medicine including: brain imaging, labeling of blood elements, and identifying fatty infiltration of organs. A tropolone-gallium complex has been characterized by the determination of in vitro partition ratios correlated with in vivo organ distribution in the rat. Partition ratios were determined for gallium-67 citrate, indium-114m chloride, and iron-59 chloride cations complexed with tropolone in chloroform + water, octanol + water, olive oil + water, and olive oil + plasma two-phased systems. Tropolone proved to be highly effective in the lipid solubilization of these metal cations. Distribution studies in animals of these cations complexed with tropolone demonstrated an increased concentration of these cation complexes in tissues of high lipid content when compared with appropriate controls.
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