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At least 379 records · Page 21Linked to original sources
PubMed1984

Self- and allo-specific suppressor T cells evoked by intravenous injection of F protein.

The liver/serum protein F appears to inactivate clones reactive towards itself in the T helper cell but not the B cell compartment. To examine the extent of self-reactivity in the T suppressor cell compartment, the well-established procedure of i.v. injecting milligram doses of the protein was used. To detect suppression, an entirely in vitro proliferation assay was devised, based on use of immunopurified F antigen. In this way T suppressor cells could be detected after activation either by allogeneic F, or (though to a lesser extent) by self-F protein. Thus the T suppressor cell compartment contains potentially self-reactive clones, and to that extent the receptor repertoire of T suppressor cells overlaps with B rather than T helper cells.

Animals↗
PubMed1984

Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432.

Mouse spleen cells, either pretreated in vitro with 100 U/ml of OK-432-induced IFN gamma for 18 h or obtained from mice 24 or 48 h after i.v. injection of OK-432(100 micrograms/mouse), were examined for their anti-tumor effect by Winn's neutralization assay against Meth-A tumor cells in BALB/c mice. Spleen cells treated in vitro or obtained in vivo 24 h after i.v. injection clearly neutralized the growth of admixed Meth-A cells. Two booster injections of 200 U of IFN gamma near the tumor site accelerated this neutralizating effect. In order to determine the effector subpopulation, inhibitory spleen cells were treated with either anti-Thy-1 monoclonal antibody plus complement, anti-asialo GM1 serum plus complement or with adherence on plastic plates followed by Sephadex G-10 column treatment. The effector cell activity in Winn assay was lost only after the removal of macrophages through plastic plate adherence and Sephadex G-10 column treatment, but not after anti-Thy-1 or anti-asialo GM1 treatment, with either in vitro- or in vivo-treated spleen-cell populations. The growth of Meth-A cells was inhibited not only by these activated macrophages in Winn's assay, but also by adoptive transfer of OK-432-induced cytotoxic macrophages intralesionally 4 days after the implantation of 1 X 10(6) Meth-A cells. Our evidence suggests that the systemic action of OK-432 can be explained by the effect of induced IFNgamma, through the activation of macrophages.

Animals↗
PubMed1984

Distribution and elimination of coated polymethyl [2-14C]methacrylate nanoparticles after intravenous injection in rats.

Surfactant-coated polymethyl [2-14C]methacrylate nanoparticles had significantly different time-course distribution patterns in rats than noncoated and albumin-coated particles. Blood concentrations of poloxamer 188-coated particles were 70-fold higher after 30 min, and the particles persisted at higher levels in the circulation for up to 2 h. The initial and final liver levels were significantly lower (38% after 30 min, 51% after 7 d) and spleen levels were significantly higher (21% after 30 min, 23% after 7 d) than non-coated particles (74% in the liver and 5% in the spleen after 7 d) and the albumin-coated particles (84% in the liver and 5% in the spleen after 7 d). Specific activity was somewhat higher for the surfactant-coated particles in other organs such as the lungs, kidneys, testicles, ovaries, and lymph nodes. The bovine serum albumin sorption behavior of polymethyl methacrylate nanoparticles was followed under various conditions, and adsorption was found to increase with increasing protein concentration and increasing temperature, reaching a maximum at the isoelectric point of pH 4.9 after approximately 12 h of incubation. The zeta potential of the particles decreased with increasing pH, and the change was more pronounced with the albumin-coated particles.

Animals↗
PubMed1994

Localization of prothymocytes from wild-type and viable motheaten mice following intravenous injection into irradiated adoptive recipients.

Bone marrow cells from viable motheaten (me(v)) mutant mice fail to repopulate the thymus of irradiated recipients upon i.v. adoptive transfer. This defect can be corrected by the addition of wild-type marrow to the me(v)/me(v) marrow prior to i.v. injection. The present study focused on the nature of this apparent defect in me(v)/me(v) prothymocyte activity. We established an adoptive transfer assay system that facilitated the investigation of the migration patterns of wild-type and me(v)/me(v) marrow prothymocytes in adoptive recipients. Wild-type prothymocytes were found to seed the thymus of recipients as early as 1 day after i.v. injection. This early wave of prothymocyte seeding peaked at 4 days and diminished to undetectable levels at 6 days postinjection. After an interval of no detectable wild-type precursor activity in the thymus of primary recipients, a second wave of activity was observed on Day 15. This second wave resulted in permanent engraftment and persisted throughout the observation period. In contrast, only one initial wave of me(v)/me(v) prothymocyte seeding occurred in the recipient thymus. Detection of mev/mev precursors in the recipient's thymus was dependent upon the coinjection of wild-type marrow cells. These results suggest that me(v)/me(v) prothymocytes initially seed to the thymus of adoptive recipients, but fail to proliferate and/or differentiate due to a defect in marrow-derived intrathymic accessory cell activity.

Animals↗
PubMed1980

Pulmonary localization of intravenously injected liposomes.

Clearance from the circulation and tissue distribution of liposomes of differing size, surface charge, and composition injected IV into BALB/c mice have been examined. Large (500-3,400 nm diameter) liposomes are cleared from the circulation more rapidly than small sonicated liposomes (less than 100 nm diameter). Negatively charged liposomes are cleared more rapidly than neutral or positively charged liposomes of the same size. The major site at which liposomes injected IV accumulate, irrespective of their composition, is the liver. Accumulation of liposomes at extrahepatic sites, such as the lung, is influenced by liposome size, charge, and composition. Optimal localization and retention of liposomes in the lung were achieved with large negatively charged multilamellar and reversed evaporation phase liposomes containing phosphatidylserine (PS/PC, 3:7 mol ratio; PS/PC/LL 4.95:4.95:0.1 mol ratio).

Injections, Intravenous↗
PubMed1980

Distribution of Bratton-Marshall-positive material in mice following intravenous injections of nitrosoureas.

As determined by a colorimetric assay measuring parent compounds plus ether-extractable nitroso-containing metabolites, N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) disappeared more rapidly than N-(2-chloroethyl)-N'cyclohexyl-N-nitrosourea (CCNU) and N-(2-chloroethyl)-N'-(4-transmethylcyclohexyl)-N-nitrosourea (MeCCNU) and their products from the tissues of mice injected IV. Assay of selected samples by high-pressure liquid chromatography revealed that the colorimetric assay for BCNU was specific in that the two assays gave equivalent results. Following IV-injections of CCNU and MeCCNU, however, levels of the parent compounds decreased much more rapidly than the total, color-producing material. Of seven tissues, the largest Cxt values for BCNU, as determined by the colorimetric assay, were noted for blood (442 microgram-min/ml) and large intestine (285 microgram-min/g). Liver (29 microgram-min/g) had the lowest Cxt value, reflecting rapid metabolism of the compound by this organ. Color-producing material related to CCNU disappeared from the solid tissues of mice in a manner generally parallel to that for blood. Of the Cxt values for this compound and its products, those for lung (1753 microgram-equivalents-min/g), kidney (1633 microgram-equivalents-min/g), and small intestine (1557 microgram-equivalents-min/g) were highest. Consistent with its slower rate of metabolism, MeCCNU and its color-producing metabolites remained in most tissues of mice for 12 h following injection. Except for brain (1434 microgram-equivalents-min/g), Cxt values for this nitrosourea and its metabolites in tissues were higher than those of blood (5485 microgram-equivalents-min/ml), with kidney (15,324 micrograms-equivalents-min/g), liver (12,921 microgram-equivalents-min/g), and large intestine (11,501 microgram-equivalents-min/g) being highest. For each nitrosourea, a fair correlation was observed between the Cxt values for tissues and the toxic and/or antitumor effects at those sites.

Animals↗
PubMed1983

Pharmacokinetics of melphalan in children following high-dose intravenous injection.

The pharmacokinetics of high-dose IV melphalan (140 or 220 mg m-2) were studied after 12 administrations in 10 children (aged 2.5-16 years) undergoing chemotherapy for either neuroblastoma or Ewing's tumour. To assess whether a simpler and less expensive nitrobenzylpyridine (NBP) spectrophotometric assay for alkylating activity was a satisfactory alternative to high-pressure liquid chromatography (HPLC), the plasma melphalan concentration was estimated by both methods in five cases. Analysis of the disposition of melphalan gave a mean half-life of 1.3 +/- 1.0 (SD) h, clearance 18.4 +/- 9.4 l X h-1 X m-2, and apparent volume of distribution 26.3 +/- 18.0 l X m-2. These pharmacokinetic parameters were similar to those found in adults: no correlation was found between any parameter and age or glomerular filtration rate. NBP alkylating activity determinations yielded consistent results and good correlation with plasma melphalan concentration. However, concordance analysis indicated a consistent bias, the NBP assay always giving lower estimates of plasma melphalan concentration: HPLC assay therefore remains the method of choice for determining plasma melphalan pharmacokinetics.

Adolescent↗