Background: Differences in protein interactions between wild-type and mutant huntingtin are relevant to the disease. Results: Mutant huntingtin interacts with unique proteins and alters the subcellular context of some interactions shared with wild type. Conclusion: Mutant Huntington disease protein has loss-of-function and gain-of-function attributes. Significance: Results implicate understudied proteins and cellular/molecular processes that may contribute to the onset of the Huntington disease pathology.

The quantitative proteomic analysis of complex protein mixtures is emerging as a technically challenging but viable systems-level approach for studying cellular function. This study presents a large-scale comparative analysis of protein abundances from yeast protein lysates derived from both wild-type yeast and yeast strains lacking key components of the Snf1 kinase complex. Four different strains were grown under well-controlled chemostat conditions. Multidimensional protein identification technology followed by quantitation using either spectral counting or stable isotope labeling approaches was used to identify relative changes in the protein expression levels between the strains. A total of 2388 proteins were relatively quantified and more than 350 proteins were found to have significantly different expression levels between the two strains of comparison when using the stable isotope labeling strategy. The stable isotope labeling based quantitative approach was found to be highly reproducible among biological replicates when complex protein mixtures containing small expression changes were analyzed. Where poor correlation between stable isotope labeling and spectral counting was found, the major reason behind the discrepancy was the lack of reproducible sampling for proteins with low spectral counts. The functional categorization of the relative protein expression differences that occur in Snf1-deficient strains uncovers a wide range of biological processes regulated by this important cellular kinase.

The raw carp bile has both nephrotoxic and hepatotoxic effects which are not well known. Recently, we studied 13 patients who had toxic acute renal failure and toxic hepatitis after ingestion of raw bile of carp in 3, grass carp in 8 and silver carp in 2 cases. The purpose of this report is to alert physicians to this very rare cause of toxic acute renal failure and hepatitis. All patients presented initially with gastrointestinal upset after eating. These symptoms were followed by oliguria in 7 patients (54%), hematuria was noted in 10 (77%) and jaundice in 8 patients (62%). Elevation of blood urea nitrogen, creatinine and transaminases lasted for about 3 weeks. The severity of the symptoms depended on the amount of bile ingested. All the patients recovered with conservative therapy and hemodialysis. Biopsy of the kidney revealed findings compatible with acute tubular necrosis similar to that produced by other nephrotoxins. Biopsy of the liver revealed findings consistent with acute toxic hepatitis. Both suggest toxic effects of carp bile as a cause of toxic acute renal failure and hepatitis.

Analysis of the five different serum isoenzymes of lactate dehydrogenase (LDH) is of great value in the differential diagnosis of various diseases. In order to investigate the changes of serum LDH isoenzymes in several renal diseases, 44 patients with Korean hemorrhagic fever, 10 patients with chronic renal failure, 10 patients with nephrotic syndrome, and 15 healthy subjects were studied. The isoenzymes of LDH were determined by the Helena LDH isoenzyme electrophoresis procedure. LDHl was 22.3 ± 2.8, LDH2 29.4 ± 5.1, LDH3 20.8 ± 4.5, LDH4 9.0 ± 2.7 and LDH5 8.8 ± 3.2 mU/ml in healthy subjects. In patients in the oliguric stage of Korean hemorrhagic fever, LDHl was 63.4 ± 28.5, LDH2 99.7 ± 40.7, LDH3 107.5 ± 39.0, LDH4 41.9 ± 32.8 and LDH5 37.2 ± 26.3 mU/ml, while LDHl was 23.8 ± 11.7, LDH2 38.9 ± 14.6, LDH3 36.0 ± 18.7, LDH4 13.8 ± 13.0 and LDH5 12.7 ± 7.6 mU/ml in nonoliguric patients. In patients with chronic renal failure LDH1 was 33.2 ± 10.8, LDH2 41.9 ± 13.3, LDH3 27.7 ± 8.5, LDH4 12.1 ± 6.2 and LDH5 12.3 ± 5.8 mU/ml. In patients with nephrotic syndrome, LDH1 was 25.1 ± 4.3, LDH2 33.5 ± 4.9, LDH3 23.1 ± 6.2, LDH4 8.4 ± 3.7 and LDH5 8.4 ± 3.4 mU/ml. In summary, LDH3 activity was elevated in the oliguric stage of Korean hemorrhagic fever and LDH2 was elevated in chronic renal failure; those values were correlated with the BUN level.

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