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Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment 总被引:4,自引:0,他引:4
The antenatal variant of Bartter's syndrome is an autosomal recessive
kidney disease characterized by polyhydramnios, premature delivery,
hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous,
having been linked recently to mutations in an ATP- sensitive, renal outer
medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl
co-transporter, NKCC2. We characterized four of the mutations reported in
three heterozygous ROMK variants of antenatal Bartter's and found that each
expressed a distinct phenotype in Sf9 cells. One mutation expressed normal
function and appears to be an allelic polymorphism. The other three
mutations produced channels with significantly reduced K+fluxes. However,
the mechanisms in each case were different and reflected abnormalities in
phosphorylation, proteolytic processing or protein trafficking. The
different mechanisms may be important in the design of appropriate therapy
for patients with this disease.
相似文献
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H. J. Stein M.D. W. K. H. Kauer M.D. H. Feussner M.D. J. R. Siewert M.D. EA.C.S. 《Journal of gastrointestinal surgery》1998,2(4):333-341
Bile reflux has been implicated in the pathogenesis and malignant degeneration of Barrett’s esophagus, but clinical studies
in patients with adenocareinoma arising in Barrett’s esophagus are lacking. Ambulatory esophageal measurement of acid and
bile reflux was performed with the previously validated fiberoptic bilirubin monitoring system (Bilitec) combined with a pH
probe in 20 asymptomatie volunteers, 19 patients with gastroesophageal reflux disease (GERD) but no mucosal injury, 45 patients
with GERD and erosive esophagitis, 33 patients with GERD and Barrett’s esophagus, and 14 patients with early adenocarcinoma
arising in Barrett’s esophagus. Repeat studies were done in 15 patients under medical acid suppression and 16 patients after
laparoscopie Nissen fundoplication. The mean esophageal bile exposure time showed an exponential increase from GERD patients
without esophagitis to those with erosive esophagitis and benign Barrett’s esophagus and was highest in patients with early
carcinoma in Barrett’s esophagus (P <0.01). Pathologic esophageal bile exposure was documented in 18 (54.5%) of 33 patients
with benign Barrett’s esophagus and 11 (78.6%) of 14 patients with early adenoearcinoma in Barrett’s esophagus. Nissen fundoplieation
but not medical acid suppression resulted in complete suppression of bile reflux. Bile reflux into the esophagus is particularly
prevalent in patients with Barrett’s esophagus and early cancer. Bile reflux into the esophagus can be completely suppressed
by Nissen fundoplication but not medical acid suppression alone. (J GASTROINTEST SURG 1998;2:333-341.)
Presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14,
1997 相似文献
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Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity 总被引:1,自引:0,他引:1
Micropipette aspiration tests on single erythrocytes have previously shown that the static rigidity (membrane shear modulus) of oxygenated sickle cells increased with increasing hemoglobin concentration, whereas the rigidity of normal cells was independent of hemoglobin concentration. Moreover, it was observed that after mechanical extension, sickle cells exhibited persistent deformation more frequently and to a greater extent than normal cells. To ascertain if differences in association of normal and sickle hemoglobin with the membrane could account for these observations, we measured rheologic properties of normal membranes reconstituted with sickle hemoglobin and sickle membranes reconstituted with normal hemoglobin. The static rigidity of normal ghosts reloaded with sickle hemoglobin was higher than those of either normal ghosts reloaded with normal hemoglobin or native normal cells. On the other hand, the increased rigidity of native sickle cells decreased to near-normal values following reconstitution with normal hemoglobin. Furthermore, we observed that normal ghosts reconstituted with sickle hemoglobin exhibited persistent bumps after mechanical extension, but no bumps formed on normal ghosts reconstituted with normal hemoglobin. Moreover residual bumps were not produced on sickle cells reloaded with normal hemoglobin. Since mechanical characteristics peculiar to sickle cells could be induced in normal cells by incorporation of sickle hemoglobin, and since normal characteristics could be restored to sickle cells by incorporation of normal hemoglobin, we suggest that the interaction of sickle hemoglobin with the cell membrane is responsible for augmented static rigidity of oxygenated sickle erythrocytes. 相似文献
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