Biomedical subjects
Publications and source records attributed to S Sparrow.
From a survey of breeding records of the AGUS/ Lac rat colony, 1% of animals weaned were found to lack tails. Post-mortem examination of 5 females showed major skeletal and genital abnormalities. Tailless rats were found more often than expected in 4th and 5th litters. A 'threshold' model of inheritance was postulated with an unknown environmental factor 'triggering' the condition.
Male Porton-Wistar rats, 32 weeks old, were given i.p. one of the following doses of HgCl2; 0.5, 1.0 or 1.5 mg Hg/kg. In the preceding 4-week period and throughout the experiment the animals had free access to either tap water or 1.0% saline. The urinary excretion of alkaline phosphatase measured in urine samples, collected during the first 24 h after treatment with mercury, indicated that chronic saline loading significantly attenuated tubular damage caused by 0.5 mg or 1.0 mg Hg/kg, but not by 1.5 mg Hg/kg. Tubular necrosis 12 and 24 h after mercury was also less severe and extensive in saline than in tap water-drinking rats. This difference was still noticeable 4 days after mercury treatment in rats dosed with 0.5 mg Hg/kg, but death in the two higher dose groups prevented further pair-to-pair histological comparison. At the selected dose levels chronic saline loading did not decrease renal mercury content at 12 or 24 h and therefore protection was not associated with decrease in renal mercury uptake. The experiment indicates that chronic saline drinking, which at higher doses attenuates HgCl2-induced acute renal failure but not tubular necrosis, is able to moderate the severity of tubular necrosis when the dose of HgCl2 is as low as 0.5 mg Hg/kg. This protective effect diminishes as the dose is increased.
Distribution of individual mitotic phases in different human xenografts on nude mice showed significant changes after treatment with a range of drugs when compared with untreated controls. The total amount of mitoses in prophase significantly decreased in all responsive tumors while those in all other phases increased but in a very variable degree. There was some correlation in between the range of the mitotic phase distribution changes and the degree of tumor response to treatment.
Wide range of different drugs used in the cytotoxicity studies in an amelanotic human melanoma xenograft on nude mice showed a clear inverse relationship between melanogenesis and proliferation. Decreasing rates in proliferative activity estimated by mitotic answer expressed by phase distribution changes as well as by the tumor volume response to drug treatment were in direct relationship with increasing rates in the degree of melanogenesis expressed in percentage of melanin containing cells in histological specimens.
The acute renotoxicity of HgCl2 and phenylmercuric acetate (PhHgAc) was compared at two intraperitoneal dose levels: 0.5 and 1.0 mg Hg/kg. There was no difference in the type of proximal tubular damage caused by the two mercurials, but 1.0 mg Hg/kg as PhHgAc produced approximately the same degree of damage as 0.5 mg Hg/kg as HgCl2. At the selected dose levels only HgCl2, but not PhHgAc increased the urinary excretion of alkaline phosphatase. At 12 and 24 h after PhHgAc the content of mercury was higher in blood and lower in the kidneys and urine than after the administration of equimolar doses of HgCl2. As the difference in the rectal mercury contents of HgCl2 and PhHgAc treated groups declined with time, difference in renotoxicity seems to relate only to renal mercury taken up within 24 h of administration. It is suggested that the slower renal extraction of mercury - as in regenerating kidneys (Tandon and Magos 1980) - was responsible for the lower degree of renotoxicity in phenylmercury treated rats.
This is the third report of a prospective study of children with sex chromosome anomalies identified at birth in New Haven, Connecticut. Previous reports in 1974 [1] and 1979 [2] summarized data from the first 2 1/2 years and the first 9 years of the children's lives, respectively. The present report will focus on progress and evaluations in the years 9-13, concluding with an Appendix of Case Summaries which provide an overview of 6 of the cases. Accumulation of data from such children is increasingly important to assist in genetic counseling. Because of the rarity of sex chromosome aneuploidy (about 1 in 400 newborns), no one center sees enough of these children to feel confident about the validity of results. However, the periodic meeting, sharing of data, and joint publication of results by investigators in several centers, made possible by the March of Dimes provide large enough numbers of children with each karyotype for valid conclusions about range of expected growth and development through the preadolescent years. Therefore, this report is published together with those from other centers, as in the 1979 report [2].
Mice inoculated intranasally with murine coronaviruses (mouse hepatitis viruses) were killed daily for seven days. Lung and liver sections stained by the immunoperoxidase technique indicated that with three of the four strains examined viral localisation and replication in the lung preceded that found in the liver. Thus, infection by the respiratory route may be of importance in the transmission of these viruses.
The poathogenesis of Sendai virus and pneumonia virus of mice (PVM) was studied using the immunoperoxidase technique on paraffin lung sections. The pathology of Sendai virus corresponds to that of a bronchopneumonia, with virus demonstrated by immunoperoxidase in the bronchial epithelium, and sometimes in macrophages, for a period of 2--9 days post-infection. Pneumonia virus of mice produces an interstitial pneumonia with virus demonstrated in the bronchial epithelium but also in the alveolar walls and alveolar macrophages. This virus can be demonstrated between 2 and 7 days post-infection. This technique was used to demonstrate PVM in the case of a natural outbreak of this disease and may eventually become a routine technique for the screening of lung tissue for respiratory viruses.
The pathogenicity and persistence of pneumonia virus of mice (PVM) and Sendai virus has been studied using germ-free nu/nu mice. PVM was found to infect cells of the bronchial epithelium (and the alveolar wall) of the lungs of germ-free nu/nu mice using the immunoperoxidase technique. The virus was located in the bronchial epithelium for 11 days before elimination, but persisted in the alveolar wall for the duration of the experiment (20 days). After Day 10 a humoral antibody response to PVM was observed which persisted, although at a low level (1 in 40), by haemagglutination-inhibition (HI) testing. Sendai virus in nu/nu mice also infected cells of the bronchial epithelium and this persisted for the duration of the experiment (27 days). The persistence of virus in the bronchial epithelium in relation to lack of humoral antibody is discussed with reference to local secretory antibody production, especially since this does not occur with PVM.
The pathogenesis of Sendai virus infection was studied in athymic and AGUS rats. The infection was more severe in the athymic rats and caused considerable clinical disease. Virus was shown to replicate in the bronchial epithelium and persisted in athymic rats for the duration of the experiment (32 days). The characteristic changes of necrosis of the bronchial epithelium and subsequent hyperplasia also persisted in this group and was accompanied by quite extensive interstitial pneumonitis. The virus failed to evoke an antibody response in the athymic rats.
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The incidence of clinical viral disease in mice, hamsters, rats, guinea-pigs and rabbits in the United Kingdom in 1976--1977 is recorded. The significance of these diseases is discussed and recommendations for their control are made.