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)

Water channel aquaporin-1 (AQP1) is strongly expressed in kidney in proximal tubule and descending limb of Henle epithelia and in vasa recta endothelia. The grossly normal phenotype in human subjects deficient in AQP1 (Colton null blood group) and in AQP4 knockout mice has suggested that aquaporins (other than the vasopressin-regulated water channel AQP2) may not be important in mammalian physiology. We have generated transgenic mice lacking detectable AQP1 by targeted gene disruption. In kidney proximal tubule membrane vesicles from knockout mice, osmotic water permeability was reduced 8-fold compared with vesicles from wild-type mice. Although the knockout mice were grossly normal in terms of survival, physical appearance, and organ morphology, they became severely dehydrated and lethargic after water deprivation for 36 h. Body weight decreased by 35 +/- 2%, serum osmolality increased to >500 mOsm, and urinary osmolality (657 +/- 59 mOsm) did not change from that before water deprivation. In contrast, wild-type and heterozygous mice remained active after water deprivation, body weight decreased by 20-22%, serum osmolality remained normal (310-330 mOsm), and urine osmolality rose to >2500 mOsm. Urine [Na+] in water-deprived knockout mice was <10 mM, and urine osmolality was not increased by the V2 agonist DDAVP. The results suggest that AQP1 knockout mice are unable to create a hypertonic medullary interstitium by countercurrent multiplication. AQP1 is thus required for the formation of a concentrated urine by the kidney.
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PMID:Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. 946 75

Although intrinsic pituitary lesions are the most common cause of hypopituitarism, suprasellar masses can produce similar symptoms. The differential diagnosis of a suprasellar mass includes cystic lesions, tumors, granulomatous disease, and infection. The etiology is not always obvious, and despite extensive work-up, may remain elusive. A 28-year-old Mexican man presented with complaints of headache and weakness for two weeks duration. He became increasingly lethargic and an MRI revealed a two centimeter suprasellar mass. Testing of the hypothalamic-pituitary axis suggested panhypopituitarism. He was prescribed treatment with hydrocortisone, DDAVP, and levothyroxine. Open craniotomy and biopsy of the hypothalamus revealed marked inflammation with plasma cells, histiocytes, and small lymphocytes. Light microscopy revealed macrophage-contained leishmania-like organisms although results were not immediately available. Pathological data was consistent with acute infection by Trypanasoma cruzi. Despite supportive efforts, the patient expired two months after presentation. This case illustrates the difficulty of diagnosing and the potential rapid mortality of a suprasellar mass. Because of the wide consideration of etiologies, a tissue diagnosis is needed. However, as this case illustrates, a definitive tissue diagnosis is not always possible, even following biopsy during open craniotomy.
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PMID:Acute chagas' disease presenting with a suprasellar mass and panhypopituitarism. 1576 61