Effect of in utero irradiation on the postnatal development, behavior, and brain structure of rats: dose fractionation with a 6-h interval.

Based on previous studies showing that exposure of the rat fetus to ionizing radiation produces dose-dependent (0.25-1.25 Gy) changes in postnatal development of behavior and decreases in the thickness of the cerebral cortex, we examined the extent to which dose fractionation would reduce expression of damage. Pregnant rats were exposed to single doses of 0.5 or 1.0 Gy, or to two doses of 0.5 Gy 6 h apart on day 15 of gestation. Offspring were subjected to four behavioral tests on postnatal days 7-28; the rats were then sacrificed and their brains removed and processed for histology. For all end points, the fractionated dose produced an effect that was intermediate between that of the 0.5- and 1.0-Gy doses and which, by interpolation, could be expressed as equivalent to a single dose between 0.5 and 1.0 Gy. The equivalent single dose was not significantly different from the 1.0-Gy dose for negative geotaxis (0.54 Gy), reflex suspension (0.80 Gy), and continuous corridor (0.85 Gy). For sine of the angle of the advance of hind feet (0.58 Gy), width of stride (0.69 Gy), length of stride (0.75 Gy), body weight (0.73 Gy), and cerebral cortex thickness (0.69 Gy), the fractionated dose produced effects significantly different (P < 0.05) from the 1.0-Gy dose. Overall, exposure of fetal rats to two doses of 0.5 Gy separated by 6 h produced effects equivalent to a single dose of 0.70 Gy, as measured by postnatal behavioral tests and morphological assessment of brain structure.

Cytokine regulation of cellular proliferation in endometriosis.

OBJECTIVE: This study was designed (1) to characterize the resident leukocyte population in ectopic endometrium (EE), (2) to assess proliferative activity of cellular components in EE, (3) to assess whether resident leukocytes in EE express IFN gamma mRNA and (4) to demonstrate endometrial epithelial cell IFN gamma receptors in EE. STUDY DESIGN: Biopsies of EE and normal eutopic endometrium (UE) were studied immunocytochemically using monoclonal antibodies specific for CD45 leukocyte common antigen, CD3 (a T cell marker), CD11c (a macrophage marker), and Ki67 (proliferation marker). Leukocyte types were identified immunocytochemically, followed by in situ hybridization to assess expression of IFN gamma mRNA. IFN gamma receptor expression was assessed by immunocytochemistry. RESULTS: The percentage of scattered stromal cells staining for each CD marker was greater in EE than in UE. The proliferative activity of endometrial stromal cells and epithelial cells was significantly less in EE than in UE. The overall concentration of T cells and macrophages expressing IFN gamma mRNA was significantly greater in EE than in UE. The percentage of each leukocyte type expressing IFN gamma mRNA was also greater in EE than in UE, and IFN gamma receptors were present in glandular epithelium of EE. CONCLUSIONS: These findings support a possible paracrine role for resident leukocytes and IFN gamma in regulating cell proliferation in endometriosis.

Effect of in utero radiation dose fractionation on rat postnatal development, behavior and brain structure: 3-hour interval.

Effect of In Utero Radiation Dose Fractionation on Rat Postnatal Development, Behavior and Brain Structure: 3-Hour Interval. Neurotoxicology 15(1): 183-190, 1994. We have previously shown that exposure of the rat fetus to ionizing radiation produces dose-dependent (0.25-1.25 Gy) changes in postnatal growth and behavior, and decreases in cerebral cortex thickness. Pregnant rats were exposed to single doses of 0.5 or 1.0 Gy, or to two doses of 0.5 Gy (separated by a 3 h interval) on gestational day 15. Pups were weighed and subjected to behavioral tests (righting reflex; reflex suspension; negative geotaxis; continuous corridor; and length, width, and sine of gait) over postnatal days 7-28. The rats were then sacrificed and brains removed for histology. The fractionated doses produced responses that were generally intermediate between those produced by the single doses and which, by interpolation, could be expressed as equivalent to a single dose between 0.5 and 1.0 Gy. Overall, exposure of the fetal rat to two doses of 0.5 Gy separated by 3 h produced effects equivalent to a single dose of 0.85 Gy. We conclude that fractionation of radiation dose results in less damage to the developing rat cerebral cortex, as measured by postnatal growth, behavioral tests, and morphological assessment.

Enhanced expression of resident leukocyte interferon gamma mRNA in endometriosis.

PROBLEM: Previous studies have shown that the endometrial epithelial/stromal cell proliferative activity of endometriosis is significantly less than that of normal endometrium and that the concentration of resident stromal leukocytes is significantly greater in ectopic than in eutopic endometrium. Other work has shown that interferon gamma (IFN gamma), secreted by resident leukocytes, inhibits endometrial cell proliferation in vitro. Accordingly, we hypothesized that the lower proliferative activity of endometriosis may be related to enhanced resident leukocyte IFN gamma production. This study was designed to assess whether resident leukocytes in endometriosis express IFN gamma mRNA and to compare this expression to that of normal endometrium. METHODS: Biopsies of ectopic endometrium (N = 16) from women in the follicular phase and normal proliferative (N = 9) and secretory (N = 8) endometria were examined for IFN gamma expression. Using monoclonal antibodies specific for CD45 (leukocyte common antigen), CD3 (a T-cell marker) and CD11c (a macrophage marker), leukocyte types were identified immunocytochemically, followed by in situ hybridization to examine expression of IFN gamma mRNA. RESULTS: Results demonstrated that (1) the overall concentration of T cells and macrophages expressing IFN gamma mRNA is significantly greater in endometriosis as compared to eutopic endometrium, and (2) the percent of each leukocyte type expressing IFN gamma mRNA is greater in endometriosis than in normal endometrium. CONCLUSIONS: These findings support a possible paracrine role for resident leukocytes in regulating cell proliferation in endometriosis.