Although gentamicin (GM) has been used widely as an antibiotic, the specific binding protein of the drug has not yet been understood sufficiently. Here we show that GM specifically associates with the 73-kDa molecular chaperone HSP73 and reduces its chaperone activity in vitro. In the present study, we investigated GM-specific binding proteins using a GM-affinity column and porcine kidney cytosol. After washing the column, only the 73-kDa protein was eluted from the column by the addition of 10 mM GM. None of the other proteins were found in the eluant. Upon immunoblotting, the protein was identical to HSP73. Upon CD spectrum analysis, the binding of GM to HSP73 resulted in a conformational change in the protein. Although HSP73 prevents aggregation of unfolded rhodanese in vitro, the chaperone activity of HSP73 was suppressed in the presence of GM. Using limited proteolysis of HSP73 by TPCK-trypsin, the GM binding site is a COOH-terminal for one third of the protein known to be a peptide-binding domain. During immunohistochemistry, HSP73 and GM were co-localized in enlarged lysosomes of rat kidneys with GM-induced acute tubular injury in vivo. Our results suggest that the specific association between HSP73 and GM may reduce the chaperone activity of HSP73 in vitro and/or in vivo, and this may have an interaction with GM toxicity in kidneys with GM-induced acute tubular injury.
We report a 66-year-old male who developed diabetic ketoacidosis (DKA) and necrosis of the small intestine due to nonocclusive mesenteric ischemia (NOMI), 3 months after starting quetiapine treatment. He was transferred to our hospital and diagnosed as diabetic for the first time, associated with DKA. Despite improvement in DKA, abdominal pain worsened gradually 10 h after hospitalization. Computed tomography (CT) revealed bowel emphysema, and gas out of the gut wall, in the mesenteric veins and the intrahepatic portal vein, suggesting intestinal necrosis. He survived because of resection of necrotic small-intestinal tissue and he finally required no diabetes treatment. Mesenteric arteries were patent with good palpitation without occlusion or thrombosis, and pathological findings showed ischemic enteritis, which is consistent with NOMI. DKA is a rare but serious side effect of second-generation antipsychotic medications (SGAMs) such as quetiapine, which can result in NOMI: a life-threatening complication. We must keep in mind that the plasma glucose concentration may increase in patients taking SGAMs, or that NOMI may occur concurrently if DKA develops.
A 5-month-old boy was referred to our department to examine poor development of external genitalia. The patient was diagnosed with micropenis and bilateral impalpable testes, and testosterone replacement therapy was recommended. The testes remained impalpable at 14 months of age; therefore, laparoscopy was performed to explore intraabdominal testes. The patient was incidentally diagnosed with congenital unilateral absence of the right vas deferens.A renal sonography performed after the operation revealed a high possibility of right renal agenesis. Congenital absence of the vas deferens is associated with a high probability of renal anomalies. It is, therefore, essential to pay careful attention to renal dysfunction.
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