RESUMEN
Hypoxia stimulates angiogenesis in some microvascular beds, but no clear angiogenic effect of hypoxia has yet been demonstrated in adult skeletal muscle. In this study the distribution of alkaline phosphatase (APase) was compared with a novel microvascular marker, Griffonia simplicifolia I (GSI), to determine whether the respective markers were expressed by muscle capillaries during hypoxic conditions and to probe for the presence or absence of angiogenesis in response to short-term hypoxia. Mice were exposed to normobaric 8% oxygen for 7 or 21 days. Capillary density in the red and white areas of the gastrocnemius muscle was determined with the use of a double-labeling procedure for both APase and fluorescently tagged GSI. Little change in capillary density was found. Focal reductions in APase activity were observed within 1 wk of hypoxia, but no changes were observed in GSI binding. In controls, 74 and 92% of red and white muscle capillaries, respectively, were APase positive. This percentage declined to 60% in red and 43% in white muscle after 21 days of hypoxia. The results indicate that APase expression is labile under certain conditions and warrant a cautious approach to using the enzyme as a marker. Binding of the GSI lectin to muscle capillaries appeared to be unchanged by the exposure to hypoxia, indicating stability of this marker system. No significant change in the number of capillaries around individual muscle fibers was evident at 21 days when GSI was used to detect capillaries. These results confirm the absence of hypoxia-induced angiogenesis in muscle capillaries during the time period studied.
Asunto(s)
Fosfatasa Alcalina/biosíntesis , Músculos/enzimología , Consumo de Oxígeno/fisiología , Animales , Capilares/enzimología , Femenino , Histocitoquímica , Ratones , Ratones Endogámicos C57BL , Músculos/irrigación sanguíneaRESUMEN
Nucleated bone marrow cell numbers in normal and polycythemic mice were determined using 3H-thymidine (3H-TdR). The cellularities were estimated by extrapolating the exponential disappearance of labeled cells after a single injection of 3H-TdR to the time of injection. Dermestid beetles (Anthrenus piceus) were used to prepare tissue-free skeletons labeled with 3H-TdR. The correlation between tritium activity in bone marrow DNA and tritium derived from the combusted skeleton was determined. The total skeletal cellularity determined by isotope dilution analysis in both normal and polycythemic mice was 2.6 x 10(8) cells/mouse or 17.6 x 10(9) cells/kg body weight. Although the red cell component of the marrow was reduced in the polycythemic mouse, the total numbers of nucleated cells in both types of animals were similar. The differential distribution of cells in the polycythemic animal showed a twofold increase in granulocytic cells, which may explain the identical nucleated cell count in normal and in polycythemic mice.
Asunto(s)
Células de la Médula Ósea , ADN/metabolismo , Policitemia/patología , Timidina/metabolismo , Tritio , Animales , Recuento de Células , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Técnica de Dilución de RadioisótoposRESUMEN
Mean survival times were increased an average of 23, 53 and 61%, when 10, 15, and 20 mg/kg, respectively, of the organoplatinum congener, malonato(1,2-diaminocyclohexane) platinum(II)(NSC-224964), was given as the only treatment modality to BDF1 mice bearing 1-day-old L1210 leukemia. When a single dose of 10 mg/kg was combined with either 300 or 100 R on day 1 only, the anticipated response (ILS = 30 and 38%, respectively) based on the additive effects of the single modalities was surpassed by 26 and 21%, respectively (i.e. extent of therapeutic synergism). When divided doses of radiation (200 R/day x 3 days) were combined with 15 or 20 mg/kg of NSC-224964, survival times were enhanced an average of 15% (extent of synergism) greater than would be expected if these modalities were acting through an additive process(es).
Asunto(s)
Antineoplásicos/uso terapéutico , Leucemia L1210/terapia , Compuestos Organometálicos/uso terapéutico , Platino (Metal)/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Ciclohexanos/administración & dosificación , Ciclohexanos/uso terapéutico , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Estudios de Evaluación como Asunto , Leucemia L1210/mortalidad , Leucemia L1210/radioterapia , Ratones , Compuestos Organometálicos/administración & dosificación , Platino (Metal)/administración & dosificación , Dosificación RadioterapéuticaRESUMEN
Treatment of mice on four consecutive days with either erythropoietin (EP) or rabbit antimouse thymocyte serum (ATS) resulted in a significant reduction in antigenic reactivity of spleen cells as measured by the Simonsen assay. In normal animals, treatment with either EP or ATS resulted in lymphopenia and in most instances a neutrophilia and a variable monocytopenia. Similar alterations in these cell types were recorded for polycythemic mice subsequent to treatment with either EP or ATS. These data plus histologic analyses support the idea that there is an inverse relationship between the cells committed to differentiate along the lymphoid cell line and the cells committed to differentiate along myeloid cell lines. Further, the data are consistent with the "carrying capacity" concept regarding the stem cell microenvironment and support the monophyletic theory.