Well, good results wrt AIDS hasn't hurt PGNX today. Some of this seems like sour grapes. They are accusing Ho of making some pretty amateurish mistakes that he hasn't made. That said, it's entirely possible that there's more to CAF than three interacting defensins.
Meanwhile, back at the toxicology ranch . . . a study that was no fun for the rats:
>>Electrophoresis 2002 Sep;23(18):3241-51
Application of surface-enhanced laser desorption/ionization technology to the detection and identification of urinary parvalbumin-alpha: A biomarker of compound-induced skeletal muscle toxicity in the rat.
Dare TO, Davies HA, Turton JA, Lomas L, Williams TC, York MJ.
Clinical Pathology, Cellular and Biochemical Toxicology, Safety Assessment, GlaxoSmithKline Research and Development, Ware, Hertfordshire, UK.
In toxicity studies, compound-induced changes are typically evaluated using a combination of endpoints and there are often a number of potential markers in biological fluids which can indicate toxic change in tissues and organs. However, some biomarkers are not specific to the organ of injury and therefore there is a continuing search for more sensitive and specific indicators of target organ toxicity. In experiments to assess the potential diagnostic usefulness of surface-enhanced laser desorption/ionization (SELDI) ProteinChip(R) technology, skeletal muscle toxicity was induced in Wistar Han rats by administering 2,3,5,6-tetramethyl-p-phenylenediamine (TMPD). The skeletal muscle toxicity was monitored using established endpoints such as increase in serum aldolase (Aldol), aspartate aminotransferase (AST) and histopathology, and also using SELDI retentate chromatography mass spectrometry of urine samples. Clear differences in urinary protein patterns between control and TMPD-treated animals were observed on the ProteinChip surfaces. Additionally a specific urine marker protein of 11.8 kDa was identified in TMPD-dosed rats, and the detection of the marker was related to the degree of skeletal muscle toxicity assessed by recognized clinical pathology endpoints. The 11.8 kDa protein was identified as parvalbumin-alpha. These experiments demonstrated the potential of urinary parvalbumin-alpha as a specific, noninvasive, and easily detectable biomarker for skeletal muscle toxicity in the rat and the potential of SELDI technology for biomarker detection and identification in toxicology studies.<<
Rats probably not fond of this target search, either:
>>Gene Expr 2002;10(4):165-77
Profiling of acyl-CoA oxidase-deficient and peroxisome proliferator Wy14,643-treated mouse liver protein by surface-enhanced laser desorption/ionization ProteinChip Biology System.
Chu R, Zhang W, Lim H, Yeldandi AV, Herring C, Brumfield L, Reddy JK, Davison M.
Department of Functional Genomics, Aventis Pharmaceuticals, Inc., Bridgewater, NJ 08807, USA. ruiyin.chu@aventis.com
Peroxisome proliferators induce hepatic peroxisome proliferation and hepatocellular carcinomas in rodents. These chemicals increase the expression of the peroxisomal beta-oxidation pathway and the cytochrome P-450 4A family, which metabolizes lipids, including fatty acids. Mice lacking fatty acyl-CoA oxidase (AOX-/-), the first enzyme of the peroxisomal beta-oxidation system, exhibit extensive microvesicular steatohepatitis, leading to hepatocellular regeneration and massive peroxisome proliferation. To investigate proteins involved in peroxisome proliferation, we adopted a novel surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology to compare the protein profiles of control (wild-type), AOX-/-, and wild-type mice treated with peroxisome proliferator, Wy-14,643. The results indicated that the protein profiles of AOX-/- mice were similar to the wild-type mice treated with Wy14,643, but significantly different from the nontreated wild-type mice. Using four different ProteinChip Arrays, a total of 40 protein peaks showed more than twofold changes. Among these differentially expressed peaks, a downregulated peak was identified as the major urinary protein in both AOX-/- and Wyl4,643-treated mice by SELDI. The identification of MUP was further confirmed by two-dimensional electrophoresis and liquid chromatography coupled tandem mass spectrometry (LC-MS-MS). This SELDI method offers several technical advantages for detection of differentially expressed proteins, including ease and speed of screening, no need for chromatographic processing, and small sample size.<<
I like the sentence about using four different protein chips.
Cheers, Tuck |
