Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042024 (incontinence)
 13,409 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 41-year-old male of citrullinemia associated with argininosuccinate acid synthetase deficiency. He was admitted to the Hitachi General Hospital because of finger tremor, restlessness and urinary incontinence. He had short stature and a poor appetite. Laboratory evaluation was summarized as follows: mild hypoglycemia, low plasma cortisol levels, delayed response of 17-OHCS and 17-KS to ACTH administration in urine, and delayed response of plasma ACTH level to insulin administration. In this case, ACTH deficiency is estimated to be a dysfunction of the hypothalamus. Replacement therapy of hydrocortisone improved his symptoms. He was readmitted to the hospital because of delirium and confusion, two weeks after the hydrocortisone administration. At that time, he had flapping tremor. Laboratory examination revealed hyperammonemia (NH3: 231 micrograms/dl) and mild elevation of GOT and GPT. Serum and urinary amino acid determination showed marked elevation of citrulline (478.1 nmol/ml in serum, 4681.2 mumol/day in urine). Lactulose administration, low protein diet and plasmapheresis were started, but he went into a coma. Without any improvement, he died on the 29th hospital day. Autopsy examination of the liver disclosed fatty change. Adrenal cortex depicted severe atrophy. Biochemical analysis of urea cycle enzymes of the liver and kidney showed decreased activity of argininosuccinate synthetase (liver: 0.0022 U/mg protein, 5% of that normal liver, kidney: 0.003 IU/mg protein, 20% of that in normal kidney). Citrullinemia associated with ACTH deficiency have not reported in the literature. It may be presumed that ACTH deficiency is concerned with the delayed onset of hyperammonemia. The relation between citrullinemia and endocrinological abnormalities is also discussed.
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PMID:[A case of citrullinemia associated with isolated ACTH deficiency, rapidly developing coma]. 133 25

Prostate cancer is the leading form of malignancies among men in the U.S. While surgery carries a significant risk of impotence and incontinence, traditional chemotherapeutic approaches have been largely unsuccessful. Hormone therapy is effective at early stage, but often fails with the eventual development of hormone-refractory tumors. We have been interested in developing therapeutics targeting specific metabolic deficiency of tumor cells. We recently showed that prostate tumor cells specifically lack an enzyme (argininosuccinate synthase, or ASS) involved in the synthesis of the amino acid arginine(1). This condition causes the tumor cells to become dependent on exogenous arginine, and they undergo metabolic stress when free arginine is depleted by arginine deiminase (ADI)(1,10). Indeed, we have shown that human prostate cancer cells CWR22Rv1 are effectively killed by ADI with caspase-independent apoptosis and aggressive autophagy (or macroautophagy)(1,2,3). Autophagy is an evolutionarily-conserved process that allows cells to metabolize unwanted proteins by lysosomal breakdown during nutritional starvation(4,5). Although the essential components of this pathway are well-characterized(6,7,8,9), many aspects of the molecular mechanism are still unclear - in particular, what is the role of autophagy in the death-response of prostate cancer cells after ADI treatment? In order to address this question, we required an experimental method to measure the level and extent of autophagic response in cells - and since there are no known molecular markers that can accurately track this process, we chose to develop an imaging-based approach, using quantitative 3D fluorescence microscopy(11,12). Using CWR22Rv1 cells specifically-labeled with fluorescent probes for autophagosomes and lysosomes, we show that 3D image stacks acquired with either widefield deconvolution microscopy (and later, with super-resolution, structured-illumination microscopy) can clearly capture the early stages of autophagy induction. With commercially available digital image analysis applications, we can readily obtain statistical information about autophagosome and lysosome number, size, distribution, and degree of colocalization from any imaged cell. This information allows us to precisely track the progress of autophagy in living cells and enables our continued investigation into the role of autophagy in cancer chemotherapy.
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PMID:Quantitative analysis of autophagy using advanced 3D fluorescence microscopy. 2366 32