Protective effect of artificially induced ‘hibernation’ against lethal doses of whole body x-irradiation in CF1 male mice

1959 ◽  
Vol 196 (6) ◽  
pp. 1211-1213 ◽  
Author(s):  
Sondra M. Kuskin ◽  
S. C. Wang ◽  
Roberts Rugh

Hypothermia induced by the use of neuroplegic drugs such as Hydergine, chlorpromazine or promethazine, followed by refrigeration, does not significantly enhance the protective action afforded by refrigeration alone against the lethal dose of whole body x-irradiation in CF1 male mice. The neuroplegic drugs, without refrigeration, provide a slight degree of protection, probably due to the slight reduction in the body temperature. It appears that the action of hypothermia as a protective mechanism depends not on depression of metabolism alone, but on a general depression of bodily processes. Urethane, in conjunction with refrigeration, appears to augment the lethal effect of x-irradiation in the CF1 strain of male mice.

1960 ◽  
Vol 198 (6) ◽  
pp. 1352-1354 ◽  
Author(s):  
Roberts Rugh ◽  
Erica Grupp

Sixty CF1 mice were given 600 r whole body x-irradiation, a dose calculated to kill 30% in 30 days. Half were isolated as controls and the remaining half were provided with an adequate number of nonpregnant, mature females for daily matings for the next 30 days. The controls showed 33% lethality while the experimentals, aggravated by frequent sexual activity, showed 73% lethality. Sexual activity more than doubled the lethal effect of 600 r x-rays. Litters derived from x-irradiated, sexually active males mated during the 1st week resulted in an average of 3.1; matings during the 2nd week produced an average of 2.7 (normal control size is 9.6). Matings during weeks 3–7 were sterile. Fertility was recovered by some at 8 weeks (litter size, 6.9) and by some as late as 75 days. Control x-irradiated males, after resumption of fertility, produced litters of 7.3.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Frederique B Yiannikouris ◽  
Genevieve Nguyen

Objectives: Recent studies demonstrated that the prorenin renin receptor (PRR) is present in adipose tissue. In adipose tissue stromal cells, PRR has the ability to bind renin and prorenin and contributes to the generation of angiotensinI (AngI). However, the contribution of adipocyte PRR to the generation of the vasoactive peptide, AngII and therefore to the regulation of blood pressure in physiological condition is unknown. The purpose of this study was to develop and characterize a new mouse model with adipocyte-specific PRR deficiency and define the role of adipose PRR in normal physiology. Methods and results: Female mice with 2 loxP sites flanking exon 2 of the PRR gene (floxed alleles, PRRfl/fl) were bred with aP2-Cre or with Adi-Cre male mice. Since PRR is located in the X chromosome, the male mice generated from the breeding were homozygotes for the deletion (PRRaP2 and PRRAdi). From the breeding, 5 PRRfl/fl, 2 PRRaP2 and 5 PRRAdi male mice were generated suggesting that the deletion of PRR in adipocyte was not lethal. Mice were fed on chow diet during 20 weeks. The body weight, the fat, lean mass and the blood pressure were quantified. Preliminary data suggest that the body weights (BW) were slightly decreased in PRRaP2 and PRRAdi compared to PRRfl/fl (PRRfl/fl: 29±1g; PRRaP2: 25±5g; PRRAdi: 28±1g). The slight reduction in BW was attributed to a reduction in fat mass (PRRfl/fl: 4.8±0.9g; PRRaP2: 3.8±1.8g; PRRAdi: 1.9±0.4g). Blood pressure was measured by plethysmography and by radiotelemetry. Preliminary data demonstrated that under physiological conditions, the SBP was not changed in PRRaP2 male mice compared to PRRfl/fl mice (plethysmography: PRRfl/fl: 108±1 mmHg; PRRaP2: 99±7 mmHg; radiotelemetry: PRRfl/fl: 129±2 mmHg; PRRaP2: 128±6 mmHg). The SBP of PRRAdi is currently under investigation. Conclusions: These results demonstrate the viability of mice with specific adipocyte deficiency of PRR. Future studies will define the effects of adipocyte PRR deficiency on obesity-induced hypertension.


1963 ◽  
Vol 41 (2) ◽  
pp. 347-360 ◽  
Author(s):  
P. V. Vittorio ◽  
E. W. Wight ◽  
B. E. Sinnott

Studies were carried out to determine the effect of X-irradiation on the uptake of chromium 51 in different organs in the mouse. Experiments were also carried out to determine whether the initial radiation effect, if any, was lessened or the return to normal chromium 51 uptake accelerated when the animal was treated with a specific radioprotective agent (serotonin) prior to exposure to X-irradiation. If the assumption is made that early disturbances in Cr51content in different organs are a measure of the effect of various treatments and the return to normal Cr51content a measure of recovery, the results obtained could be indicative of changes caused by X-irradiation and those prevented or caused by serotonin.


1912 ◽  
Vol 16 (1) ◽  
pp. 78-102 ◽  
Author(s):  
Augustus B. Wadsworth

From the results of this study of the action of immune sera on pneumococcus infection it is evident that immune sera vary greatly in their curative value. Immune sera possess protective action, but protective action is not necessarily indicative of curative action. Treatment with the serum of normal rabbits may prolong the course of pneumococcus infection in the rabbit. This action, however, is slight and not always manifest. Sera from animals immunized with dead pneumococcus cells which had been washed free from their products, failed to exert materially greater curative action than normal sera. Sera from animals immunized with culture filtrates free from pneumococcus cells possessed, in some instances, a slight curative value, but often this curative action was not apparent. In animals actively immunized, however, the presence of an immunity to culture filtrates was readily demonstrated. In the immunity produced by injections of dead culture material the strength was not sufficiently exalted for the sera to possess a practical curative value. It was only after immunization with virulent living cultures that the blood serum acquired marked curative action. After pneumococcus infection in the rabbit had become established, treatment with this serum induced crisis and cured the animals. From the results of the study of the mechanism of recovery it is evident that, despite the fact that virulent pneumococci are singularly insusceptible to the action of immune sera in the test-tube, pneumococcus infection nevertheless conforms to the general law of infection. Diphtheria and tetanus organisms give rise to powerful toxins, but the parasitism of these organisms is slight and their development is localized. Diseases produced by these organisms are toxemias and neutralization of their toxins by antitoxin puts an end to the disease. The pneumococcus gives rise to toxic substances which are less active or are active only in the body tissues, but the parasitism of this organism is marked and its development is rarely localized. Nevertheless, the manifestations of the disease arise from the action of the bacterial poisons on the tissues. The neutralization of the pneumococcus poisons by immune serum puts an end to the symptoms of the disease, but the pneumococci survive as harmless parasites until destroyed by lysis or phagocytosis. The neutralization of the pneumococcus poison may take place suddenly and completely as in crises; or, it may be incomplete with exacerbations of infection, as in lysis. Crisis, as it occurs in the lobar pneumonia of man and in the bacteriemia of the rabbit, is simply one phase of recovery, and recovery does not differ fundamentally, whether it is sudden and complete as in crisis, or incomplete and prolonged as in lysis, or whether the pneumococci are destroyed by lysis extracellularly as in the rabbit, or intracellularly as in the phagocytosis of the dog and man. Since the recovery of animals from pneumococcus infection differs in no essential from that of man, since the unaided protective mechanism of man as compared with that of susceptible animals is exceptionally efficient, and since it is possible by treatment with sera from animals highly immunized with living cultures of virulent pneumococci to cure pneumococcus infection in the most susceptible animals, it is difficult to conceive of the infection in man failing to yield similarly to the administration of such sera.


1973 ◽  
Vol 59 (2) ◽  
pp. 97-118 ◽  
Author(s):  
Vincenzo Covelli ◽  
Pietro Metalli ◽  
Bruno Bassani ◽  
Benito Di Caterino ◽  
Giovanni Silini

Life-long observations on untreated animals have shown that spontaneous reticulum cell sarcomas (RCS) developed in 56.5 % male mice of the hybrid (C57BL/Cne x C3H/Cne) F1 strain; the average age at death of mice with tumors was 949 days, compared with 929 days for all causes: no age-specific peak of mortality has been shown to occur over the entire life span of the animals. Histologically, the spleen and all the lymphnodes, including the mesenteric node, were always invaded; neoplastic growth was found less frequently in kidneys, liver and lungs (77, 70, and 40%, respectively), only occasionally in other organs such as adrenals and testes, and never in the thymus. The tumor was predominantly composed of a single type of neoplastic cells, resembling highly undifferentiated reticular cells, typically proliferating from the periarteriolar region of the lymphatic follicles in the spleen. The monomorphic aspect of the tumor cell population suggests that RCS in this strain of mice may be classified as type A according to Dunn. Electron-microscopy observations showed the presence of a few virus-like particles both in tumor cells and in sediments from cell-free extracts. Transplantation of cells from spontaneous RCS into both normal and lethally-irradiated syngeneic recipients was successful only in 4 out of 7 experiments, regardless of the tissue of origin of the neoplastic cells (spleen, lymphnodes or bone marrow). Virus-like particles were seen with higher frequency in transplanted tumors. Inoculation of cell-free extracts into neonatal mice of low-leukemia strains has not so far been successful. Splenectomy of young animals as well as the intravenous injection of syngeneic bone marrow cells immediately following a lethal dose of whole-body X-irradiation significantly reduced the frequency of spontaneous tumors.


1957 ◽  
Vol 189 (1) ◽  
pp. 15-20 ◽  
Author(s):  
D. C. Jones ◽  
D. J. Kimeldorf ◽  
G. K. Osborn ◽  
T. J. Castanera ◽  
D. O. Rubadeau

Shielding of the abdomen during x-irradiation was used to test the hypothesis that the initial decrease in the volitional activity of rats observed after whole-body x-irradiation is related primarily to irradiation of the abdomen. Exposure of the abdomen to 200 r, or of the remaining half of the body to 200 or 600 r did not result in a significant depression in activity. When the abdomen was exposed to 600 or 750 r, however, a depression in activity was observed, with a minimum on the 3rd day postirradiation, followed by increasing activity. When animals were exposed to relatively high doses (1500 or 2000 r) with the abdomen shielded, or with only the head exposed (1500 r), there was an immediate depression in activity on the 1st day postirradiation, then a transient increase in activity to values equal to or well above control levels, followed by a rapid decrease below control activity, and then by increasing activity. The transient increase above control activity was duplicated by pair-feeding nonirradiated animals to the head-exposed group. It appears that the initial decrease in volitional activity may be mediated by altered gastrointestinal function, particularly with respect to the 3rd day postirradiation. In abdomen-shielded or head-exposed animals subjected to higher doses of x-rays, the transient rise in activity appears to be related to restricted food intake, probably as a result of radiation damage of the oral mucosa. The subsequent depression in volitional activity in these animals may be related to central nervous system injury.


1959 ◽  
Vol 196 (2) ◽  
pp. 441-444 ◽  
Author(s):  
Leonard J. Cole

Previous studies have shown that the injection of spleen cells from normal adult parental strain (A-strain) mice into sublethally x-irradiated (500 r) F1 hybrid mice ((LxA)F1), elicits delayed deaths in 100% of the animals. This lethal effect is elicited, as shown here, also by spleen cells from adult L-strain mice, but not by spleen cells derived from newborn (1–2-day-old) parental strain mice. Following supralethal whole-body x-irradiation (870 r) of LAF mice, the injection of cells from spleen or liver of newborn A-strain mice afforded up to 100% protection against death by 30 days postirradiation; no late ‘homologous deaths’ were seen in the mice which received spleen cells from the newborn A-mice, in contrast with that observed when hematopoietic cells from adult A-mice are injected. The data imply that spleen cells from newborn mice are immunologically nonreactive, and lend further support to the hypothesis that late homologous deaths (in the context employed here) results primarily from an immunological reaction of the injected cells against the host.


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