Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inoculation of three- to four-week-old BALB/c mice with temperature-sensitive (ts) vesicular stomatitis virus mutant G41 produced a subacute neurological disease, initially characterized by development of lethargy, hunched posture, and ruffled fur within five to seven days after infection. More than 90% of infected mice developed these clinical signs. In approximately 60% of infected mice, the initial neurological signs proceeded to striking hind-limb paralysis and weight loss. These signs usually appeared by seven to nine days after infection and lasted for 21-28 days. Only 16% of the mice died as a result of infection; death usually occurred eight to 12 days after infection. Most of the infected mice recovered from the acute phase of disease and appeared normal by four weeks after infection. However, hind-limb paralysis persisted in 4% of the mice for as long as the mice were observed, i.e., 42 days. The mutant ts-G41 was recovered from the brains and spinal cords of infected mice for the first seven days after infection. Peak titers of virus were modest, 10(4)-10(5) pfu/ml in brain tissue and 10(3)-10(4) pfu/ml in spinal cord tissue. Virus isolated after in vivo infection was temperature-sensitive and thus not revertant wild-type virus. Although virus was recoverable by homogenization for only the first seven days of infection, use of cocultivation techniques permitted the detection of ts-G41 in brains and spinal cords of infected animals for as long as 21 days after infection. Virus recovered by cocultivation was also temperature-sensitive.
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PMID:Subacute infection with temperature-sensitive vesicular stomatitis virus mutant G41 in the central nervous system of mice. I. Clinical and virologic studies. 22 Mar 28

Serum sickness in man may occur after treatment with foreign proteins such as tetanus or diphtheria antisera, and in some patients leads to neurological complications such as neuropathy or encephalomyelitis. Many of the effects of serum sickness are associated with the deposition of antigen-antibody complexes in the tissues. Chronic serum sickness in the rabbit has previously been shown to cause perivascular inflammation and demyelination in the nervous system. We induced chronic serum sickness in the Lewis rat by daily intraperitoneal injections of bovine serum albumin (BSA) in male rats that had previously received footpad inoculations of BSA. Two animals died of anaphylaxis and 15 were observed for periods of 39 to 142 days. Three animals injected with 3 mg or 4 mg/day of BSA, and 6 animals injected with up to 16 mg/day of BSA had no clinical abnormalities when sacrificed. Six animals were injected with 36 to 40 mg BSA/day and, at the time of sacrifice, were lethargic and had ruffled fur, but no neurological signs. In these animals, the production of chronic serum sickness was confirmed by the presence of immune complex deposits in the kidneys. In the nervous system, there was no evidence of inflammatory cell infiltration either in the parenchyma or the vessel walls. Immunofluorescence studies identified deposits of immunoglobulin in the choroid plexus of chronic serum sickness rats but not in controls. Staining with antibodies to immunoglobulin, complement and BSA showed marked staining of blood vessels of the nerve roots of the animals with chronic serum sickness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of neurological abnormalities in Lewis rats with experimental chronic serum sickness. 182 22

The time course of morphologic changes in the influenza B mouse model of Reye's syndrome is described and compared to the clinical, virologic, and biochemical changes. Following an intravenous inoculation of a lethal dose of an egg adapted strain of influenza B/Lee/40 virus, mice first showed clinical signs of lethargy and ruffled fur at 12 hours (h) post inoculation (pi). The earliest morphologic changes in the liver occurred at 12 h pi, and consisted of a slight increase in fat and loss of glycogen in hepatocytes. Over the next 36 h, the accumulation of microvesicular fat increased, and mitochondrial abnormalities such as pleomorphism and loss of dense bodies developed. There was no increase in peroxisomes. In the brain, focal cerebral edema was detected as early at 6-12 h pi. The edema, manifested as swelling of astrocytic foot processes, increased in severity with time. Endothelial cells were not abnormal. Myelin sheath splitting rarely was observed. Since changes occurred simultaneously in the liver and in the brain, we suggest that influenza B virus caused a simultaneous primary insult to both organs.
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PMID:The sequence of changes in liver and brain in the influenza B virus mouse model of Reye's syndrome. 217 2

In the present study we investigated the role of mononuclear phagocytes in the pathogenesis of lipopolysaccharide (LPS)-induced lethality and tissue injury. Since hepatic and splenic macrophages are the primary sites of localization of i.v.-injected LPS, we selectively eliminated these macrophages using liposome-encapsulated dichloromethylene diphosphonate (DMDP). After double DMDP-liposome treatment the phagocytic cells in the liver and spleen were completely eliminated, except for the macrophages in the white pulp of the spleen which were affected to a lesser extent by this treatment. An i.v. injection of LPS into DMDP- and saline-pretreated mice showed that the latter animals exhibited febrile-associated symptoms such as lethargy and ruffled fur, but that macrophage elimination abrogated these symptoms. Although after double saline- or DMDP-pretreatment the LD50 appears to be 1 mg and 630 micrograms, respectively, the differences in lethality between both groups of mice were not statistically significant. Therefore, we concluded that hepatic and splenic macrophages are not necessary for LPS-induced lethality. The role of macrophages in LPS-induced local tissue damage was studied by comparing the histopathological changes in hepatic and splenic tissue between DMDP- and saline-pretreated mice. A sublethal dose of LPS induced similar hepatic lesions in macrophage-depleted and saline-pretreated mice, whereas the histopathological changes in the spleen were much more pronounced after DMDP-pretreatment. Particularly in the inner periarteriolar lymphocyte sheath (PALS) of these mice, the number of T cells was considerably reduced and extensive cellular necrosis could be found. These data strongly suggest that the local tissue damage resulting from LPS injection may not be due to its localization in mononuclear phagocytes but rather to interaction with other cell types.
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PMID:The role of macrophages in LPS-induced lethality and tissue injury. 296 1

Antitumor effects of i.v. injected human recombinant tumor necrosis factor (rTNF) against solid Meth A tumors in mice appeared to be critically dependent on the dose and were limited by its toxicity. Extensive necrosis and complete cures were only induced by doses having untoward effects, such as diarrhea, hypothermia, ruffled fur, and lethargy. Murine tumor necrosis serum (TNS, 0.5 ml) had about the same antitumor potential and induced all side effects except diarrhea. More extensive necrosis and approximate doubling of the incidence of complete regression in the absence of gross side effects were observed upon administration of a low dose of rTNF combined with detoxified endotoxin, nontoxic poly A:U, or submicrogram doses of toxic endotoxin. The separate constituents had little antitumor effects, if any at all. Increasing the dose of toxic endotoxin resulted in a further potentiation of necrosis, overt toxicity, but no cures. Muramyl dipeptide and interferon alpha/beta did not potentiate effects of rTNF. In vitro growth of Meth A cells was not inhibited by toxic endotoxin, rTNF or the combination, although TNS was highly inhibitory. Data show that therapeutic effects of rTNF and its synergy with endotoxin are not due to direct effects on the tumor cells and that the extent of prompt in vivo tumor necrosis does not predict the course of tumor growth. Therapeutic effects of both TNS and toxic endotoxin probably involve a synergy between low levels of TNF and other factors/effects induced by endotoxin. Detoxified endotoxin and poly A:U probably induce the latter effects and little or no TNF, so explaining the absence of side effects, their weak antitumor potential, and their powerful synergistic action with rTNF. A role for interferon alpha/beta as an induced synergistic factor is not likely. Muramyl dipeptide and TNF might share properties needed for synergy with endotoxins.
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PMID:Synergistic action of human recombinant tumor necrosis factor with endotoxins or nontoxic poly A:U against solid Meth A tumors in mice. 382 51

1-Amino-2,4-dibromoanthraquinone (ADBAQ), an intermediate in the production of commercial dyes for wool, silk, and synthetic fibers, was selected for toxicology and carcinogenesis studies in two rodent species. In advance of the 2-year studies, 13-week studies were conducted in male and female F344/N rats and B6C3F1 mice which were fed a diet containing ADBAQ at concentrations of 0, 0.25, 0.50, 1.00, 2.50, and 5.00%. ADBAQ stained the skin and fur red at all doses in rats and at 1.00% and higher concentrations in mice. Lethargy and emaciation were noted at the 2.50% and higher doses in rats of both sexes. In general, the absolute weight of the liver and the liver/organ weight ratios increased in both sexes and species at all doses. Treated rats developed a chronic toxic hepatitis characterized by hepatocytomegaly, centrilobular vacuolar degeneration and necrosis, regenerative nodules, acute necrotizing cholangitis, bile duct hyperplasia, chronic active inflammation in periportal areas, and focal pigmentation. The hepatopathy occurred at all doses in males and at 0.50% and higher in females and correlated with elevations of serum glutamic-pyruvic and glutamic-oxaloacetic transaminases, leukocytosis, and neutrophilia. Hyaline droplet degeneration in the proximal convoluted tubules of the kidneys occurred in male rats, and uterine atrophy was observed in female rats at 1.00% and higher. Anemia occurred in both sexes of rats at all doses and thymic atrophy was observed in both sexes of high-dose rats. In male mice minimal dose-related lesions in the liver included centrilobular glycogen depletion at 1.00% and higher and pigmentation at all doses. At comparable doses, ADBAQ was considered to be markedly toxic in rats and of minimal nonlife-threatening toxicity in mice.
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PMID:Thirteen-week toxicology studies of 1-amino-2,4-dibromoanthraquinone in Fischer 344/N rats and B6C3F1 mice. 395 25

A toxin associated with Toxoplasma gondii infection was obtained from the trophozoites and culture medium used to propagate the parasite in cell cultures. The toxin, named Toxofactor (TF), administered parenterally or nonparenterally in adult mice, produces transient symptoms of lethargy, ruffled fur, and body weight loss. Organ changes which accompanied the outward symptoms included hepatosplenomegaly and involuted thymus. TF activity was detected in extracts of the blood, peritoneal fluid, liver, and spleen of infected mice. Severe damage to embryonal and fetal development was induced when TF was administered during pregnancy. Resorption, abortion, and congenital abnormalities were produced, dependent upon the stage of development at the time of exposure. Adult mice which had reacted to and recovered from an initial intraperitoneal injection to TF were protected against a secondary challenge from TF. Fetal development was also protected from damage when TF was used to challenge adults previously exposed to TF. Mouse and rabbit anti-TF sera neutralized TF activity in the adult. In no instance did control mice show any deleterious effect when exposed to soluble cell lysate from the uninfected cell line (BHK-21) used to propagate the organism plus the used medium from these same uninfected cells. TF activity was not attributed to bacterial, myocoplasmal, or viral contamination. TF toxic activity is labile to elevated temperature and high or low pH, which also destroy its protective properties. TF activity was sensitive to trypsin and was obtained in the elution fraction (alpha-methyl-D-mannoside) from affinity chromatography (concanavalin A-Sepharose 4B). Ultrafiltration indicated the molecular weight to be between 50,000 and 100,000. TF, apparently a glycoprotein, was quantitated for activity by a weight loss assay. A unit of activity was defined as the minimum quantity of TF (highest dilution) which produced at least a 10% average body weight loss in adult Nya:NYLAR female mice between days 7 and 12 post-intraperitoneal injection.
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PMID:Toxofactor associated with Toxoplasma gondii infection is toxic and teratogenic to mice. 668

The inhibitory effect of 13-cis-retinoic acid was tested in conjunction with ethyl carbamate (urethane) induced murine pulmonary adenomas. Continuous feeding of the retinoic acid for 20 weeks did not significantly reduce the number of surface adenomas. No physical evidence of toxicity due to the vitamin A analog was observed in any of the mice. All mice showed a steady weight gain during the 20-week period, and there was no evidence of eye lesions, hemorrhage, bone fractures, fur changes or lethargy.
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PMID:13-cis retinoic acid and murine pulmonary adenomas: a preliminary report. 695 75

Infected, neutropenic animals are used as experimental models to evaluate the relative efficacies of antimicrobial agents and host-pathogen-antibiotic interactions. In the past, these models used death as the study end point. Because of the concern about use of death as an end point, we evaluated the accuracy with which various signs of infection predicted mortality in a neutropenic guinea pig model of treated and untreated Pseudomonas aeruginosa sepsis. The potential surrogate markers studied included ruffled fur, respiratory distress, diarrhea, hunched posture, lethargy, abnormal neurologic movements (twitching, paralysis of a limb), inappetence for > 48 h, the inability to ambulate, and the inability of a supine animal to stand. In addition, we evaluated whether percentage of weight loss or change in daily food and water consumption were predictive of mortality. Animals were inspected for these signs at least every 4 h during the day and every 8 h in the evening. In treated and untreated animals, 100% of subjects that were unable to ambulate or to rise from the supine position died (positive predictive value for death was 100% for either sign). Guinea pigs that could not rise from a supine position expired between 1 and 8 h after this sign was observed. Those that could not ambulate died between 4 and 40 h after that sign was observed. In treated and untreated animals, none of the survivors manifested either sign of disease (100% specificity for each sign). However, 59% of untreated and 69% of treated animals that were ambulatory were found dead at the next observation period, underscoring the rapidity with which this infection progresses to death when it enters its final stage. No other signs of infection distinguished animals that survived or died. Thus, the inability of neutropenic, infected guinea pigs to rise from a supine position and the inability to ambulate were the only signs that accurately predicted death and, therefore, are the only signs that can be used as surrogates for death in this experimental model of P. aeruginosa sepsis.
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PMID:Predictive value of several signs of infection as surrogate markers for mortality in a neutropenic guinea pig model of Pseudomonas aeruginosa sepsis. 943 98

The FVB mouse is used extensively in transgenic research because of its defined inbred background, superior reproductive performance, and prominent pronuclei, which facilitate microinjection of genomic material. Seizures associated with a known mutation and seizure-susceptible inbred strains are well documented in mice; however, to the authors' knowledge, seizures in the FVB strain have not been evaluated. Affected nonmanipulated FVB/N (n = 5) and transgenic FVB/N mice generated, using eight unrelated transgenic constructs (n = 63), were submitted for pathologic examination. Most cases were detected during routine observations in animal rooms; however, seizure induction by tail tattooing, fur clipping, and fire alarms has been observed. The majority of mice were female (62 of 68), with mean age of 5.8 months (range, 2 to 16 months). Observations made during seizure presentation in 12 of 68 mice included facial grimace, chewing automatism, ptyalism with matting of the fur of the ventral aspect of the neck and/or forelimbs, and clonic convulsions that frequently progressed to tonic convulsions and death. Four mice were dead at presentation, with matting of the fur of the neck and forelimbs. The remainder of the mice had nonspecific signs of disease, such as lethargy, moribundity, or matting of the fur. Vendor and in-house animal health surveillance reports indicated that mice were seronegative to all murine pathogens. Results of gross pathologic examination were unremarkable. Microscopic findings were limited to the brain and liver. In all mice, neuronal necrosis was present in the cerebral cortex, hippocampus, and thalamus. Concurrent astrocyte hypertrophy, as evidenced by an increase in glial fibrillary acidic protein staining, was detected. Acute coagulative necrosis of centrilobular hepatocytes was present in the liver of some cases (19 of 68). Infective agents were not detected in selected brain specimens submitted for electron microscopy or in brain and liver specimens evaluated by use of special stains. Cytopathologic effect was not observed in 3T3, Vero, and BHK-21 cell lines inoculated with brain and liver specimens. The ischemic neuronal necrosis observed in these mice is consistent with lesions associated with status epilepticus in humans. The hepatocellular changes are interpreted to be agonal and associated with terminal hypoxia in seizuring animals. These results provide evidence of a previously unrecognized, often lethal epileptic syndrome in FVB mice that may have a major impact on transgenic research and other disciplines using this mouse strain.
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PMID:Neuropathologic findings associated with seizures in FVB mice. 951 87


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