Hypodontia in the beagle after perinatal whole-body 60Co gamma irradiation

As part of a long-term study to evaluate health effects of pre- and postnatal irradiation, dental development was examined. Beagles were irradiated in utero at 8, 28, or 55 days postcoitus or postnatally at 2, 70, or 365 days postpartum. Whole-body 60Co gamma radiation doses ranged from 0 to 3.8 Gy. There was an age-dependent dose-related increase in premolar hypodontia for animals irradiated at 55 days postcoitus or 2 days postpartum with doses of 0.83 Gy or higher and for those irradiated at 28 days postcoitus with 1.2 Gy or higher.     

Growth and development of mice offspring after irradiation in utero with 2,450-MHz microwaves

Mice offspring irradiated in utero with 2,450-MHz radio-frequency (RF) radiation at 0 or 28 mW/cm2 (whole-body averaged specific absorption rate = 0 or 16.5 W/kg) for 100 minutes daily on days 6 through 17 of gestation were evaluated for maturation and development on days 1, 5, 10, 12, 15, and 17 of age. The tests used to determine differences in developmental age in the two treatment groups were body weight, urine concentrating ability, brain weight, tolerance to ouabain, and bone lengths. Fifteen sham-irradiated and 26 RF-irradiated litters, normalized to eight pups/litter, were used in this study. Mean body weight of the microwave-irradiated offspring were significantly (p = .0003) decreased only on day 1 of age. Brain weight on days 10, 12, and 17 were significantly lower in microwave-irradiated pups (p = .01). There were no significant differences in the two groups in urine concentrating ability on day 5, ouabain tolerance on day 15, or bone length on days 5, 10, 12, and 17. It is concluded that there is a persistent delay in postnatal development of the brain after RF irradiation with 16.5 W/kg during gestation.     

Appearance of virus-like particles in Tritrichomonas foetus after drug treatment

Tritrichomonas foetus is a parasitic protist that infects the urogenital tract of cattle causing bovine trichomonosis. Virus-like particles (VLPs) in protozoa have been reported in several parasites including Trichomonas vaginalis, a human flagellate, but viruses were never described in T. foetus so far. Herein we show for the first time the presence of VLPs in T. foetus after several drug treatments. They were detected by electron microscopy and were confirmed by immunofluorescence microscopy using antibodies anti-virus proteins. These VLPs were always observed in clusters of variable size. Their preferential locations were at the cell periphery, close to the axostyle, and interestingly in some cases, inside the nucleus. Their appearance occurred when the parasites were under drug-treatments, such as cytoskeleton-affecting drugs (colchicine, vinblastine, taxol, nocodazole, and griseofulvin) or drugs inducing cell death, such as lactacystin and H(2)O(2). We propose that cytoskeleton participates in trichomonads of the process of virus release or maturation. These virus particles were not described previously probably because they were either in low amount or in a latent state.     

Toxicity of Trimethoprim-Sulphamethoxazole in Patients with Megaloblastic Haemopoiesis

Four consecutive patients with megaloblastic anaemia who also received therapy with trimethoprim-sulphamethoxazole all showed poor responses to specific haematinic therapy. This was attributed to trimethoprim, which suppressed reticulocyte responses in three cases and produced a pancytopenia in two and a falling haemoglobin with neutropenia in a third. A fourth patient, with pernicious anaemia, had a satisfactory reticulocyte response but experienced no clinical benefit until after withdrawal of trimethoprim.Trimethoprim seems not to be a safe form of therapy in patients with a megaloblastic process; many of the toxic reactions reported with this drug may be on the basis of an unrecognized megaloblastic form of haemopoiesis.     

Multilineage differentiation of human MSC after in utero transplantation

Prenatal transplantation of stem cells is an exciting frontier for the treatment of many congenital diseases. The fetus may be an ideal recipient for stem cells, as it is immunologically immature and has rapidly proliferating cellular compartments that may support the engraftment of transplanted cells. Mesenchymal stem cells (MSC), given their ability to differentiate among multiple lineages, could potentially be used to treat diseases such as osteogenesis imperfecta, muscular dystrophy, and a variety of others that can be diagnosed in utero. We have shown, using a human-sheep in utero xenotransplantation model, that human MSC have the ability to engraft, differentiate into many tissue types, and survive for over 1 year in fetal lamb recipients. This observation warrants further studies of the behavior of MSC following systemic or site-directed transplantation.     

Neutron irradiation of late mouse embryos (15-19 days) in utero

Pregnant female C57B1/6 mice were irradiated with a single whole-body dose of 0.5 Gy neutrons. The F1 hybrid embryos were exposed to the neutrons in utero on Day 17 +/- 2 of gestation. 178/439 (40.6%) of the irradiated fetuses and 26/217 (12%) of the control mice died within 2 weeks after birth. In both irradiated and control mice, most deaths (95 and 77%, respectively) occurred within 3 days of birth: most animals in both groups died on Day 2. There was no significant difference in the number of living young born per litter (7.2) between the neutron-irradiated mothers and their unirradiated controls. The irradiated mice weighed significantly less than their controls. On the first day after birth, body weights of mice irradiated in utero averaged only 85% of control weights. Body weights did not reach control levels until 6 months after birth. Several organs were weighed at regular intervals in both irradiated and control mice. Spleens and thymus glands showed no significant differences between the two groups. The livers and kidneys of the irradiated mice weighed slightly less than their controls. The brain weight of 21-day-old neutron-irradiated mice was 30-35% less than control brains. The weight loss of the brain was not only a relative loss, but also an absolute one, based on brain weight/body weight ratios. Histological analysis of the central nervous system showed pycnotic nuclei, inhibition of mitosis in neuroblasts, and cell death in the irradiated brains. The weight reduction of the brain was not due to water loss. Our hypothesis is that the early mortality after birth is related to the killing of the radiation-sensitive neuroblasts. When newborn mice (1-7 days old) were irradiated in vivo with the same neutron dose of 0.5 Gy, neither the reduction in brain weight nor the early mortality was observed. The early deaths of the neutron-irradiated mouse embryos does not appear to be caused by either the hematological or the gastrointestinal radiation syndrome.     

Survival and weight increase in the fetal rat after selective hypophysectomy in utero

Rat fetuses were subjected to selective hypophysectomy in utero on day 16, 17 or 18 of gestation and inspected on day 22 (the day before birth). The survival rate of fetuses operated on day 17 and 18 was about 20 and 50%, respectively. Losses were mostly caused by the surgery preceding the removal of the pituitary, and no significant survival-promoting activity of the gland could be demonstrated. The surgical injuries, as such, also reduced the weight increase substantially. Still, the loss of the pituitary was followed by a further reduction in weight gain, which on day 22 was about 10% lower than that of the sham-operated fetuses.     

Impaired insulin secretion in the neonatal rhesus monkey after chronic hyperinsulinemia in utero

The secretion of insulin by the pancreas of the newborn rhesus monkey that had been made experimentally hyperinsulinemic in utero was studied in 18 animals. Chronic in utero hyperinsulinemia was produced by the continuous subcutaneous delivery of 4.75 units of insulin per day for 18 +/- 1 days. After delivery, the insulin-containing pump was removed to allow neonatal insulin levels to drop to normal levels. By 6.5 +/- 1.0 hr after pump removal, plasma glucose, insulin, and C-peptide immunoreactivity (CPIR) were comparable in the control and experimental animals. At that point 300 micrograms of glucagon/kg body weight was given iv to stimulate insulin secretion. After 30 min a significant elevation (expressed as the percentage of basal levels) in plasma glucose by 250%, insulin by 200%, and CPIR by 200% was observed in the control animals. In contrast, no changes in plasma insulin or CPIR concentrations occurred, with an attenuated glucose response that was only one-fifth of the control response, in the experimental animals. These results along with the observed lowered concentrations of CPIR in the plasma and insulin in the pancreas at birth can be interpreted as evidence that insulin is an inhibitor of its synthesis and secretion in utero and that this abnormal intrauterine environment causes changes that persist into extrauterine life.     

Responses of the beagle to protracted irradiation. I. Effect of total dose and dose rate

The effects of protracted exposure to 60Co gamma rays on survival and tumor induction in the beagle were investigated. Total accumulated doses of 450, 1050, 1500, and 3000 cGy were given at rates of 3.8, 7.5, 12.8, and 26.3 cGy/day. Hazard models were used to identify trends in mortality associated with radiation exposure. The probability of an acute death (related to hematopoietic aplasia) was positively associated with the total dose received and the rate at which the dose was delivered. Once an animal survived the initial hematopoietic effects of radiation exposure, the risk of death from causes other than cancer, while elevated, was far less responsive than the neoplastic end points. No relationship between tumor or chronic nontumor deaths and dose rate could be identified. However, survival curves for tumor mortality did separate into a pattern clearly dependent on the accumulated dose.     

Hepatic injury after whole-liver irradiation in the rat

Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD50/30 day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [131I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract, which increase the host resistance to infection and endotoxemia, resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. The combination of these treatments resulted in additive effects leading to 38% survival at 100 days. These treatments did not, however, prevent the eventual development of radiation-induced liver pathology. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers.     

Sister-chromatid exchanges in mouse embryos after exposure to ultrasound in utero

Mouse embryos at 2 stages of development were exposed to ultrasound. The bone-marrow cells of the mother, the whole embryo, and the embryonic liver cells were analyzed. There was no consistent increase of sister-chromatid exchanges. Furthermore, the thermal effect of ultrasound did not appear to influence the frequency. Thus, ultrasound doses much higher than those used in clinical diagnosis do not induce cytogenetic damage as assayed by sister-chromatid exchanges.