Average T1 and T2 values for the ACLX knees were higher than the corresponding values for the contralateral sham operated knees following surgery (MFC data shown). A significant effect (p<0.05) for time was found for T1 data in the MFC, LFC, and MT compartments of the ACLX knee; significant differences from the 3 week group were also found in the MFC (6,12 wk), LFC (12 wk), and MT (6, 12 wk). No significant effects were demonstrated in the T1 data for the sham-operated knee. Similar effects were found for T2 data, with the addition of significant effects for time (right LT) and for 3 and 12 week differences (right LFC). A significant interaction between time and doxycycline treatment was found in the T2 data for only the LT; no significant interactions were found in any compartment for T1 . Histology demonstrates hypercellularity and disorganization suggestive of fibrocartilage formation in ACLX knees compared to sham. SPGR data is indicative of synovitis (arrow) at 3 weeks in the ACLX knees, which tends to resolve by 12 weeks (not shown), and is present to a much lesser degree in the sham-operated knees.

[PDF] [Full Text] [Abstract] , October 1, 2004; 84 (4): 1263-1314. Physiol Rev C. A. Wagner, K. E. Finberg, S. Breton, V. Marshansky, D. Brown and J. P. Geibel Renal Vacuolar H+-ATPase [PDF] [Full Text] [Abstract] , March 1, 2005; 16 (3): 1396-1405. Mol. Biol. Cell C. L. Brett, D. N. Tukaye, S. Mukherjee and R. Rao Vesicle Trafficking The Yeast Endosomal Na+(K+)/H+ Exchanger Nhx1 Regulates Cellular pH to Control [PDF] [Full Text] [Abstract] , January 1, 2006; 74 (1): 185-194. Biol Reprod and S. Breton C. Pietrement, G-H. Sun-Wada, N. D. Silva, M. McKee, V. Marshansky, D. Brown, M. Futai Epididymis Distinct Expression Patterns of Different Subunit Isoforms of the V-ATPase in the Rat [PDF] [Full Text] [Abstract] , June 1, 2006; 119 (11): 2173-2183. J. Cell Sci. C. Appenzeller-Herzog and H.-P. Hauri The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function [PDF] [Full Text] [Abstract] , August 1, 2006; 291 (2): C218-C230. Am J Physiol Cell Physiol T. E. Machen Innate immune response in CF airway epithelia: hyperinflammatory?

ABSTRACT The influences of the gastric H,-α,βcells). The pH’s of trans-Golgi network (pHTGN) and

The influences of the gastric H+/K+ pump on organelle pH during trafficking to and from the plasma membrane were investigated using HEK-293 cells stably expressing the alpha- and beta-subunits of human H+/K+-ATPase (H+/K+-alpha,beta cells). The pH values of trans-Golgi network (pHTGN) and recycling endosomes (pHRE) were measured by transfecting H+/K+-alpha,beta cells with the pH-sensitive GFP pHluorin fused to targeting sequences of either TGN38 or synaptobrevin, respectively. Immunofluorescence showed that H+/K+-ATPase was present in the plasma membrane, TGN, and RE. The pHTGN was similar in both H+/K+-alpha,beta cells (pHTGN 6.36) and vector-transfected ("mock") cells (pHTGN 6.34); pHRE was also similar in H+/K+-alpha,beta (pHRE 6.40) and mock cells (pHRE 6.37). SCH28080 (inhibits H+/K+-ATPase) caused TGN to alkalinize by 0.12 pH units; subsequent addition of bafilomycin (inhibits H+ v-ATPase) caused TGN to alkalinize from pH 6.4 up to a new steady-state pHTGN of 7.0-7.5, close to pHcytosol. Similar results were observed in RE. Thus H+/K+-ATPases that trafficked to the plasma membrane were active but had small effects to acidify the TGN and RE compared with H+ v-ATPase. Mathematical modeling predicted a large number of H+ v-ATPases (8000) active in the TGN to balance a large, passive H+ leak (with PH approximately 10-3 cm/s) via unidentified pathways out of the TGN. We propose that in the presence of this effective, though inefficient, buffer system in the Golgi and TGN, H+/K+-ATPases (estimated to be approximately 4000 active in the TGN) and other transporters have little effect on luminal pH as they traffic to the plasma membrane.