Eicosanoid production by peritoneal and splenic macrophages in mice depleted of bone marrow by 89Sr.
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Previous studies showed that the prostaglandin-forming macrophages (M phi) induced in the spleens of CBA/J mice by intraperitoneal administration of Corynebacterium parvum (CP) could not be demonstrated following the depletion of bone marrow and blood monocytes with 89Sr. The present study compares prostaglandin E2 (PGE2), leukotriene C4 (LTC4), and LTB4 release by splenic and resident peritoneal M phi in 89Sr-treated mice and 88Sr controls following in vivo CP and in vitro incubation with zymosan, calcium ionophore A23187, or phorbol ester (PMA). Intraperitoneal administration of CP resulted in the appearance of PGE2- and LTB4-releasing M phi in the spleens of control but not 89Sr mice. The incorporation and quantitative distribution of 3H-arachidonic acid into membrane lipids, however, were comparable in test and control mice. Neither zymosan nor any of the other stimulatory agents was able to effect significant release of PGE2 in vitro. No release of LTC4 by splenic M phi was detectable under experimental or control conditions. In contrast, the capacity of resident peritoneal M phi to release PGE2, LTC4, and LTB4 was apparently unaffected by 89Sr-induced bone marrow and monocyte depletion with virtually no demonstrable elicitation. Resident peritoneal M phi removed after CP in such mice showed a dramatic decrease in PGE2 release when incubated in vitro with zymosan, A23187, or PMA. These results, taken with earlier findings, demonstrate characteristically different phenotypic expression of metabolism of certain eicosanoids by splenic M phi from the spleen and the peritoneal cavity and suggest in addition that the induction of PGE2-synthesizing M phi in the spleen by CP is dependent on either an immigrant cell originating in the bone marrow or a regulatory agent derived from a bone marrow cell. (+info)
Strontium-89 therapy: measurement of absorbed dose to skeletal metastases.
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We report measurements of absorbed dose to vertebral metastases in ten patients referred for 89Sr therapy for disseminated prostatic carcinoma. Patients received a tracer dose of 85Sr at the time of 89Sr treatment and metastatic strontium retention was monitored scintigraphically for 6 mo. Metastatic 85Sr activity corrected for tissue attenuation was measured using the conjugate view principle, with special care taken to eliminate errors due to the selection of the metastatic region of interest. Metastatic volume was determined from high resolution CT images, and density inferred from Hounsfield number using the QCT bone mineral calibration of Genant and Cann. The mean absorbed dose was 850 rad/mCi (23 cGy/MBq) with a range from 220-2260 rad/mCi (6 to 61 cGy/MBq). The wide range found was consistent with the variation expected to arise due to differences in strontium renal plasma clearance (range 0.1-11.81/day) and extent of skeletal metastatic disease (varying from two small metastases to a superscan on [99mTc]MDP images) among the patients studied. (+info)
The cytokinetic behavior of pulmonary alveolar macrophages in monocytopenic mice.
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The cytokinetic behavior of pulmonary alveolar macrophages (PAM) was studied by pulse labeling with 3HTdB in mice made monocytopenic by a single intravenous injection of the bone-seeking isotope strontium-89 (89Sr). In the presence or absence of blood monocytes, PAM population size was unchanged for up to 1 month of chronic, severe monocytopenia. Pulse-labeling studies performed during monocytopenia show that in control mice PAM population half-times were 17.8 days with a potential doubling time of 39 days, whereas T1/2 was 14.8 days with a 28.5 day population doubling time for PAM in 89Sr-treated mice. Analysis of the halving times of the PAM mean grain count and the halving times of the most highly pulse-labeled cohorts suggested that PAM cell cycle times (Tc) were 5.1 days with a PAM rate of disappearance of 10.8%/day in 88Sr-treated mice and Tc of 6.6 days with a PAM rate of disappearance of 11.4%/day in 89Sr-treated mice. As measured by 3HTdR-labeling techniques, these cytokinetic values are in close approximation to each other, suggesting that 89Sr treatment did not significantly alter either PAM population size or cytokinetic behavior. Employing experimental values it was possible to construct a simple model of PAM population growth that supports the concept that the PAM population is self-renewing in the adult mouse. Taken together, the data show that a major portion of the resident PAM need not depend on the daily influx of peripheral blood monocytes to maintain themselves in a kinetically steady state. (+info)
Accumulation of radionuclides by plants as a monitor system.
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The accumulation of radionuclides by plants acting as a monitoring system in the environment may occur by two modes; foliar absorption by the leaves and shoot of the plant, or by root uptake from the soil. Data on plant accumulation of radionuclides may be obtained from studies of fission product radionuclides deposited as worldwide fallout, and from tracer studies of plant physiology. The epidermal features of plant foliage may exert an effect upon particle retention by leaves, and subsequent uptake of radionuclides from the surface. The transport of radionuclides across the cuticle and epidermis of plant leaves is determined in part by the anatomy of the leaf, and by physiological factors. The foliar uptake of fallout radionuclides, 99Sr, 131I, and 137Cs, is described with examples from the scientific literature. The environmental half-life of 131I, for example, is considerably shorter than its physical half-life because of physical and biological factors which may produce a half-life as short as 0.23/day. 99Sr and 137Cs are readily taken up by the leaf, but 137Cs undergoes more translocation into fruit and seeds than 99Sr which tends to remain in the plant part in which it was initially absorbed. Soil-root uptake is conditioned primarily by soil chemical and physical factors which may selectively retain a radionuclide, such as 137Cs. The presence of organic matter, inorganic colloids (clay), and competing elements will strongly affect the uptake of 99Sr and 137Cs by plants from the soil. The role of plants as monitors of radionuclides is twofold: as monitors of recent atmospheric releases of radionuclides; and as indicators of the long-term behavior of aged deposits of radionuclides in the soil. (+info)
Selectively eliminated blood monocytes and splenic suppressor macrophages in mice depleted of bone marrow by strontium 89.
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The contribution of specific activity to the effects of the bone-seeking isotope, strontium 89 on radiosensitive components of mononuclear phagocyte populations was investigated in mice. CBA/J mice received a fixed dose of 2 microCi/g body weight of 89Sr with three different specific activities, 6 Ci, 100 microCi and 20 microCi per mg Sr. The estimated radioactivity located in the bone surface was 4,200, 3,000 and 2,400 cpm/mg bone when measured 2 days after the administration of 89Sr, and was lost with an estimated biological half-life of 27, 25, and 23 days, respectively. Bone marrow suppression was assessed by quantitation of the depletion of macrophage-colony forming cells (M-CFC) grown in vitro in the presence of macrophage growth factor. The decline in M-CFC closely paralleled the level of radioactivity in the bone. These effects were clearly reflected by the depletion of monocytes in the blood, which were reduced to 14%, 14%, and 21% of control levels corresponding to SA's of 6 Ci/mg, 100 microCi/mg and 20 microCi/mg when counted on day 10. By day 30 the respective monocyte levels were 15%, 31%, and 77%. Furthermore, the induction of prostaglandin E producing suppressor macrophages (M phi) by Corynebacterium parvum administration was found to vary inversely with the effects of radioactivity in the bone, with initial impairment followed by quantitative recovery. Resident-type M phi in peritoneal cavity, however, appear to be unaffected by 89Sr-treatment. These data suggest, as before, that the monocytes and suppressor M phi are dependent on radiosensitive marrow cells. The observations also lead to the conclusion that the specific activity of 89Sr preparations is an important determinant of the degree of suppression and of the rate of recovery of bone marrow from the effects of irradiation that follow the administration of this isotope. (+info)
Strontium-89 therapy for the pain of osseous metastases.
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A Phase I and II study has been conducted of the safety and efficacy of 89Sr (injected i.v. as the chloride) to alleviate bone pain due to osseous metastatic disease. Potential attendant hematologic toxicity was also examined. Strontium-90 impurities were always less than 1.5%, employing a new quality control technique which detects the 90Y "daughter". Thirty-eight patients with pain due to osseous metastases requiring regular narcotic more than twice a day, documented by an abnormal bone scan and radiography, received 45 doses (1-4.5 mCi, 16-70 microCi/kg) of 89Sr after informed consent. The performance status (Karnofsky scale) ranged from 20-80%. One patient had complete pain relief while 22 other doses yielded at least a 25% reduction in narcotic requirement lasting at least 1 mo and/or 20% improvement in Karnofsky scale rating. Two patients had marked to complete relief in tumor sites which were not fractured, with no change in fracture pain. Twenty-two did not respond. Response was independent of narcotic requirements, tumor type, or Karnofsky status. No hematologic toxicity occurred. Strontium-89 may be useful as adjuvant therapy for diffuse bone pain, but a double-blind study comparing it to other nonnarcotic modalities is required. (+info)
Antigenic and biochemical characterization of the C-type particle of the stable porcine kidney cell line PK-15.
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The C-type particles observed by electron microscopy in PK-15 cells were demonstrated to have biochemical and biophysical properties associated with the oncornavirus group: density of 1:16 in a sucrose gradient, 70S RNA, and the RNA-dependent DNA polymerase. The group-specific interspecies antigen, gs-3, was not present. Evidence of a latent infection with a porcine parvovirus was also obtained. (+info)
Histochemical phosphatases and metachromasia in murine tumours induced by bone seeking radionuclides.
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Tumours induced in mice, either CBA normal and chimaerical, or C3H, by (90)Sr or (226)Ra or plutonium have been examined histochemically with (1) diazotate fast red violet LB salt in naphthol AS-MX phosphate buffer at pH 8.6 and 5.2, (2) 1: 9 dimethyl methylene blue (Taylor).It is concluded:(a) The diagnosis of osteosarcoma is facilitated with Taylor's Blue which stains osteoid metachromatically. Cells of osteosarcoma, like normal osteoblasts, contain alkaline phosphatase but this may be lost by mutation either in the original tumour or subsequently on passage of the tumour serially to compatible hosts.(b) Osteosarcomata may contain giant-cells of two forms, bizarre tumour cells and osteoclasts; the latter contain acid phosphatase. Osteosarcomata which retain their osteoid on serial passage have few cells containing acid phosphatases.(c) Primitive mesenchymal cell tumours of angiomatous form may occur, if the bone marrow is irradiated, e.g. by (90)Sr-(90)Y and Pu. These tumours lack osteoid and cells interpretable as osteoblasts or osteoclasts (though they destroy bone).(d) Tumours classifiable as fibrosarcomata occur rarely, and may be truly of fibroblastic origin or be mutated osteosarcomata.(e) Lymphomata also occur when the marrow is irradiated ((90)Sr-(90)Y and Pu). They may be generalized, when their cells may contain alkaline phosphatase or lack it. They may be localized to abdominal viscera, the reticulo-sarcomatous form, in which case the cells lack alkaline phosphatase. (+info)