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)

A 10-year-old cat that was kept on a diet consisting largely of raw liver was evaluated because of lethargy, partial anorexia, and weight loss of several months' duration. The cat's head and neck were rigidly extended, and a hard mass was palpable in the ventral cervical region. Cervical and thoracic radiography revealed proliferative bony lesions of the cervical and thoracic vertebrae as well as of the sternum and costal cartilages. Serum vitamin A concentration was 4 times normal. For reasons unrelated to hypervitaminosis A, euthanasia and necropsy were performed 6 months after evaluation. The skull and the cervical and first few thoracic vertebrae were rigidly fused, and the vertebral architecture was altered by deposition of new bone. The sternum and costal cartilages were similarly affected. The historical, physical, radiographic, laboratory, and postmortem findings were consistent with the diagnosis of hypervitaminosis A. On the basis of findings in this cat, hypervitaminosis A should be suspected in any sick cat fed a diet consisting partly or completely of raw liver.
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PMID:Hypervitaminosis A in a cat. 163 6

The developmental toxicity of glycolic acid was assessed in rats by orally administering solutions of the test material in water over days 7-21 of gestation (the day of copulation plug detection was defined as day 1 of gestation). Groups of 25 mated female Crl: CD BR rats were gavaged at daily dose levels of 0, 75, 150, 300 or 600 mg/kg. The dams were euthanized on day 22 and the offspring were weighed, sexed, and examined for external, visceral, and skeletal alterations. Clear evidence of maternal toxicity was demonstrated at 600 mg/kg; adverse clinical observations were statistically significantly increased (wheezing/lung noise, abnormal gait/staggering, lethargy). In addition, maternal body weights, weight changes, and food consumption were statistically significantly reduced at this dose level. Marginal evidence of maternal toxicity was demonstrated at 300 mg/kg; wheezing/lung noise similar to that seen at 600 mg/kg was observed in 2 of 25 dams. This increase approached statistical significance (p = 0.0553). There was marked evidence of developmental toxicity at 600 mg/kg. Mean fetal weight was statistically significantly reduced while the incidences of skeletal (ribs, vertebra, and sternebra) malformations and variations were statistically significantly increased. At 300 mg/kg/day, there was a slight (2 affected fetuses from 2 litters) increase in the incidence of two skeletal malformations: fused ribs and fused vertebra. Although these increases were not statistically significant (p = 0.0555), they were consistent with findings seen at 600 mg/kg/day and thus were considered relevant. There was no other evidence of developmental toxicity at 300 mg/kg/day nor was any developmental toxicity seen at 150 or 75 mg/kg/day. Thus, the maternal and developmental no-observed-effect level (NOEL) was considered 150 mg/kg.
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PMID:Developmental toxicity study of glycolic acid in rats. 1053 49

The Caenorhabditis briggsae homologue of the Caenorhabditis elegans pag-3 gene was cloned and sequenced. When transformed into a C. elegans pag-3 mutant, the C. briggsae pag-3 gene rescued the pag-3 reverse kinker and lethargic phenotypes. The C. elegans pag-3 gene fused to lacZ was expressed in the same pattern in C. elegans and C. briggsae. Unlike many gene homologues compared between C. elegans and C. briggsae, extensive sequence conservation was found in the non-coding regions upstream of the pag-3 exons, in several of the introns and in the downstream non-coding region. Furthermore, the splice acceptor and splice donor sites were conserved, and the size of the introns and exons was surprisingly similar. The predicted protein sequence of C. briggsae PAG-3 was 85% identical to the protein sequence of C. elegans PAG-3. Because so much of the non-coding region of pag-3 was conserved, the control of pag-3 may be quite complex, involving the binding of many trans-acting factors. These results suggest the evolutionary conservation of the pag-3 gene sequence, its expression and function.
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PMID:Conservation of sequence and function of the pag-3 genes from C. elegans and C. briggsae. 1067 14

The bivalent anti-human T cell immunotoxin A-dmDT390-bisFv(UCHT1) for treatment of patients with T cell malignancies is a single chain fusion protein composed of the catalytic domain and translocation domains of diphtheria toxin fused to two tandem sFv molecules reactive with human CD3 epsilon. This immunotoxin selectively kills CD3 epsilon positive T cells. To determine the maximum tolerated dose (MTD), pharmacokinetics and immunogenicity of A-dmDT390-bisFv(UCHT1), rat and squirrel monkey studies were performed. In both animal studies, animals received either 0, 2.5 (low), 25 (medium), or 56.25 microg/kg (high) of A-dmDT390-bisFv(UCHT1) intravenously twice daily for four consecutive days. Although transient elevation of liver transaminases in the high groups was observed, the A-dmDT390-bisFv(UCHT1) administration did not affect liver function, renal function, the hemogram, or produce serious organ histopathology. Adverse events included transient lethargy, inappetence and weight loss in high groups. A-dmDT390-bisFv(UCHT1) plasma half life was 26.95 min in rats and 18.33 min in squirrel monkeys. Immune responses to A-dmDT390-bisFv(UCHT1) were minimal in squirrel monkeys and mild in rats. In vitro cytokine release, T cell activation and CD3 epsilon receptor occupancy assays using human PBMC were further performed since rat and squirrel monkey T cells do not react with A-dmDT390-bisFv(UCHT1). A-dmDT390-bisFv(UCHT1) did not induce cytokine release or T cell activation. The A-dmDT390-bisFv(UCHT1) concentration for 50% CD3 epsilon receptor occupancy was 7.4 nM. The MTD of 200 microg/kg total provides a dose level sufficient for anti-tumor activity in vitro and in a rodent model. Therefore, we propose that this agent is a promising drug for patients with surface CD3+ T cell malignancies.
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PMID:Preclinical studies in rats and squirrel monkeys for safety evaluation of the bivalent anti-human T cell immunotoxin, A-dmDT390-bisFv(UCHT1). 1825 29