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31.
Yavuzer R Tuncer S Başterzi Y Işik I Sari A Latifoğlu O 《Plastic and reconstructive surgery》2004,113(1):34-44
The orbital floor is one of the most frequently damaged parts of the maxillofacial skeleton during facial trauma. Unfavorable aesthetic and functional outcomes are frequent when it is treated inadequately. The treatment consists of spanning the floor defect with a material that can provide structural support and restore the orbital volume. This material should also be biocompatible with the surrounding tissues and easily reshaped to fit the orbital floor. Although various autografts or synthetic materials have been used, there is still no consensus on the ideal reconstruction method of orbital floor defects. This study evaluated the applicability of solvent-preserved cadaveric cranial bone graft and its preliminary results in the reconstruction of the orbital floor fractures. Twenty-five orbital floor fractures of 21 patients who underwent surgical repair with cadaveric bone graft during a 2-year period were included in this study. Pure blowout fractures were determined in nine patients, whereas 12 patients had other accompanying maxillofacial fractures. Of the 21 patients, 14 had clinically evident diplopia (66.7 percent), 12 of them had enophthalmos (57.1 percent), and two of them had gaze restriction preoperatively. Reconstruction of the floor of the orbit was performed following either the subciliary or the transconjunctival approach. A cranial allograft was placed over the defect after sufficient exposure. The mean follow-up period was 9 months. Postoperative diplopia, enophthalmos, eye motility, cosmetic appearance, and complications were documented. None of the patients had any evidence of diplopia, limited eye movement, inflammatory reactions in soft tissues, infection, or graft extrusion in the postoperative period. Providing sufficient orbital volume, no graft resorption was detected in computed tomography scan controls. None of the implants required removal for any reason. Enophthalmos was seen in one patient, and temporary scleral show lasting up to 3 to 6 weeks was detected in another three patients. Satisfactory cosmetic results were obtained in all patients. This study showed that solvent-preserved bone, which is a nonsynthetic, human-originated, processed bioimplant, can be safely used in orbital floor repair and can be considered as another reliable treatment alternative. 相似文献
32.
Nguyen HV Stuart-Tilley A Alper SL Melvin JE 《American journal of physiology. Gastrointestinal and liver physiology》2004,286(2):G312-G320
Large volumes of saliva are generated by transepithelial Cl(-) movement during parasympathetic muscarinic receptor stimulation. To gain further insight into a major Cl(-) uptake mechanism involved in this process, we have characterized the anion exchanger (AE) activity in mouse serous parotid and mucous sublingual salivary gland acinar cells. The AE activity in acinar cells was Na(+) independent, electroneutral, and sensitive to the anion exchange inhibitor DIDS, properties consistent with the AE members of the SLC4A gene family. Localization studies using a specific antibody to the ubiquitously expressed AE2 isoform labeled acini in both parotid and sublingual glands. Western blot analysis detected an approximately 170-kDa protein that was more highly expressed in the plasma membranes of sublingual than in parotid glands. Correspondingly, the DIDS-sensitive Cl(-)/HCO(3)(-) exchanger activity was significantly greater in sublingual acinar cells. The carbonic anhydrase antagonist acetazolamide markedly inhibited, whereas muscarinic receptor stimulation enhanced, the Cl(-)/HCO(3)(-) exchanger activity in acinar cells from both glands. Intracellular Ca(2+) chelation prevented muscarinic receptor-induced upregulation of the AE, whereas raising the intracellular Ca(2+) concentration with the Ca(2+)-ATPase inhibitor thapsigargin mimicked the effects of muscarinic receptor stimulation. In summary, carbonic anhydrase activity was essential for regulating Cl(-)/HCO(3)(-) exchange in salivary gland acinar cells. Moreover, muscarinic receptor stimulation enhanced AE activity through a Ca(2+)-dependent mechanism. Such forms of regulation may play important roles in modulating fluid and electrolyte secretion by salivary gland acinar cells. 相似文献
33.
KCl cotransport is an important modulator of human cervical cancer growth and invasion 总被引:7,自引:0,他引:7
Shen MR Chou CY Hsu KF Hsu YM Chiu WT Tang MJ Alper SL Ellory JC 《The Journal of biological chemistry》2003,278(41):39941-39950
Cervical cancer is a major world health problem for women, but the pathophysiology of this disease has received scant attention. Here we show that the growth and invasion of cervical cancer cells are strongly linked the expression and activity of the KCl cotransporter (KCC), an important regulator of the ionic and cellular osmotic homeostasis. Functional assays of KCl cotransport activation by osmotic swelling, staurosporine, and N-ethylmaleimide indicate that removal of the N-terminal 117 amino acids from KCC1 produces a dominant-negative loss-of-function phenotype for KCl cotransport in human cervical cancer cells. The capability for regulatory volume decrease is much attenuated in the loss-of-function KCC mutant cervical cancer cells. The loss-of-function KCC mutant cervical cancer cells exhibit inhibited cell growth accompanied by decreased activity of the cell cycle gene products retinoblastoma and cdc2 kinase. Reduced cellular invasiveness is in parallel by reduced expression of alpha v beta 3 and alpha 6 beta 4 integrins, accompanied by decreased activity of matrix metalloproteinase 2 and 9. Inhibition of tumor growth in SCID mice confirms the crucial role of KCC in promoting cervical cancer growth and invasion. Thus, blockade of KCl cotransport may be a useful therapeutic adjunctive strategy to retard or prevent cervical cancer invasion. 相似文献
34.
Stewart AK Chernova MN Shmukler BE Wilhelm S Alper SL 《The Journal of general physiology》2002,120(5):707-722
We reported recently that regulation by intracellular pH (pH(i)) of the murine Cl-/HCO(3)(-) exchanger AE2 requires amino acid residues 310-347 of the polypeptide's NH(2)-terminal cytoplasmic domain. We have now identified individual amino acid residues within this region whose integrity is required for regulation of AE2 by pH. 36Cl- efflux from AE2-expressing Xenopus oocytes was monitored during variation of extracellular pH (pH(o)) with unclamped or clamped pH(i), or during variation of pH(i) at constant pH(o). Wild-type AE2-mediated 36Cl- efflux was profoundly inhibited by acid pH(o), with a value of pH(o50) = 6.87 +/- 0.05, and was stimulated up to 10-fold by the intracellular alkalinization produced by bath removal of the preequilibrated weak acid, butyrate. Systematic hexa-alanine [(A)6]bloc substitutions between aa 312-347 identified the greatest acid shift in pH(o(50)) value, approximately 0.8 pH units in the mutant (A)6 342-347, but only a modest acid-shift in the mutant (A)6 336-341. Two of the six (A)6 mutants retained normal pH(i) sensitivity of 36Cl- efflux, whereas the (A)6 mutants 318-323, 336-341, and 342-347 were not stimulated by intracellular alkalinization. We further evaluated the highly conserved region between aa 336-347 by alanine scan and other mutagenesis of single residues. Significant changes in AE2 sensitivity to pH(o) and to pH(i) were found independently and in concert. The E346A mutation acid-shifted the pH(o(0) value to the same extent whether pH(i) was unclamped or held constant during variation of pH(o). Alanine substitution of the corresponding glutamate residues in the cytoplasmic domains of related AE anion exchanger polypeptides confirmed the general importance of these residues in regulation of anion exchange by pH. Conserved, individual amino acid residues of the AE2 cytoplasmic domain contribute to independent regulation of anion exchange activity by pH(o) as well as pH(i). 相似文献
35.
Background
Reconstruction of the head and neck after adequate resection of primary tumor and neck dissection is a challenge. It should be performed at one sitting in advanced tumors. Defects caused by the resection should be closed with flaps which match in color, texture and hair bearing characteristics with the face. Cervicopectoral flap is a one such flap from chest and neck skin mainly used to cover the cheek defects. 相似文献36.
Petrovic S Ju X Barone S Seidler U Alper SL Lohi H Kere J Soleimani M 《American journal of physiology. Gastrointestinal and liver physiology》2003,284(6):G1093-G1103
The basolateral Cl(-)/HCO(3)(-) exchanger in parietal cells plays an essential role in gastric acid secretion mediated via the apical gastric H(+)-K(+)-ATPase. Here, we report the identification of a new Cl(-)/HCO(3)(-) exchanger, which shows exclusive expression in mouse stomach and kidney, with expression in the stomach limited to the basolateral membrane of gastric parietal cells. Tissue distribution studies by RT-PCR and Northern hybridizations demonstrated the exclusive expression of this transporter, also known as SLC26A7, to stomach and kidney, with the stomach expression significantly more abundant. No expression was detected in the intestine. Cellular distribution studies by RT-PCR and Northern hybridizations demonstrated predominant localization of SLC26A7 in gastric parietal cells. Immunofluorescence labeling localized this exchanger exclusively to the basolateral membrane of gastric parietal cells, and functional studies in oocytes indicated that SLC26A7 is a DIDS-sensitive Cl(-)/HCO(3)(-) exchanger that is active in both acidic and alkaline pH(i). On the basis of its unique expression pattern and function, we propose that SLC26A7 is a basolateral Cl(-)/HCO(3)(-) exchanger in gastric parietal cells and plays a major role in gastric acid secretion. 相似文献
37.
Role of JNK in hypertonic activation of Cl--dependent Na+/H+ exchange in Xenopus oocytes 总被引:1,自引:0,他引:1
Goss Greg G.; Jiang Lianwei; Vandorpe David H.; Kieller Dawn; Chernova Marina N.; Robertson Marilyn; Alper Seth L. 《American journal of physiology. Cell physiology》2001,281(6):C1978
In the course of studying the hypertonicity-activated iontransporters in Xenopus oocytes, we found that activation ofendogenous oocyte Na+/H+ exchange activity(xoNHE) by hypertonic shrinkage required Cl, with anEC50 for bath [Cl] of ~3 mM. Thisrequirement for chloride was not supported by several nonhalide anionsand was not shared by xoNHE activated by acid loading.Hypertonicity-activated xoNHE exhibited an unusual rank order ofinhibitory potency among amiloride derivatives and was blocked byCl transport inhibitors. Chelation of intracellularCa2+ by injection of EGTA blocked hypertonic activation ofxoNHE, although many inhibitors of Ca2+-related signalingpathways were without inhibitory effect. Hypertonicity activated oocyteextracellular signal-regulated kinase 1/2 (ERK1/2), but inhibitors ofneither ERK1/2 nor p38 prevented hypertonic activation of xoNHE.However, hypertonicity also stimulated a Cl-dependentincrease in c-Jun NH2-terminal kinase (JNK) activity. Inhibition of JNK activity prevented hypertonic activation of xoNHE butnot activation by acid loading. We conclude that hypertonic activationof Na+/H+ exchange in Xenopusoocytes requires Cl and is mediated by activation of JNK. 相似文献
38.
Functional and molecular characterization of an anion exchanger in airway serous epithelial cells 总被引:5,自引:0,他引:5
Loffing J Moyer BD Reynolds D Shmukler BE Alper SL Stanton BA 《American journal of physiology. Cell physiology》2000,279(4):C1016-C1023
Serous cells secreteCl and HCO3 and play an importantrole in airway function. Recent studies suggest that aCl/HCO3 anion exchanger (AE) maycontribute to Cl secretion by airway epithelial cells.However, the molecular identity, the cellular location, and thecontribution of AEs to Cl secretion in serous epithelialcells in tracheal submucosal glands are unknown. The goal of thepresent study was to determine the molecular identity, the cellularlocation, and the role of AEs in the function of serous epithelialcells. To this end, Calu-3 cells, a human airway cell line with aserous-cell phenotype, were studied by RT-PCR, immunoblot, andelectrophysiological analysis to examine the role of AEs inCl secretion. In addition, the subcellular location of AEproteins was examined by immunofluorescence microscopy. Calu-3 cellsexpressed mRNA and protein for AE2 as determined by RT-PCR and Westernblot analysis, respectively. Immunofluorescence microscopy identified AE2 in the basolateral membrane of Calu-3 cells in culture and rattracheal serous cells in situ. InCl/HCO3/Na+-containingmedia, the 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate(CPT-cAMP)-stimulated short-circuit anion current (Isc) was reduced by basolateral but not byapical application of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid(50 µM) and 4,4'-dinitrostilbene-2,2'-disulfonic acid [DNDS (500 µM)], inhibitors of AEs. In the absence of Na+ in thebath solutions, to eliminate the contributions of the Na+/HCO3 andNa+/K+/2Cl cotransporters toIsc, CPT-cAMP stimulated a small DNDS-sensitive Isc. Taken together with previous studies, theseobservations suggest that a small component of cAMP-stimulatedIsc across serous cells may be referable toCl secretion and that uptake of Cl acrossthe basolateral membrane may be mediated by AE2. 相似文献
39.
When injected intraperitoneally, p-chloroamphetamine (PCA) causes the acute release of catecholamines and serotonin, increases mean arterial pressure (MAP) and increases plasma renin activity (PRA) in rats. Experiments were designed to determine the dose-response and time-course for the effect of PCA administered intravenously on PRA in conscious, unrestrained rats. It was found initially that intravenous doses of PCA ranging from 0.3 - 6.0 mg/kg caused rapid and marked hypertension, but produced variable effects on PRA for up to 30 minutes after injection. In a second study PCA (0.3 - 6.0 mg/kg) did not alter PRA at 30 or 60 minutes after intravenous injection, but did increase PRA 60 minutes after 10 mg/kg, intraperitoneally. When the hypertension elicited by intravenous PCA was abolished by pretreatment with the alpha 1-adrenoceptor antagonist prazosin (100 micrograms/kg, iv), PCA produced marked elevations in PRA from 15 - 60 minutes. Thus it appeared that the renin response to intravenous PCA was masked by an elevation in MAP; when the vascular response to PCA was blocked, a large increase in PRA was observed. 相似文献
40.
Gonzalez-Begne M Nakamoto T Nguyen HV Stewart AK Alper SL Melvin JE 《The Journal of biological chemistry》2007,282(48):35125-35132
Cl(-) influx across the basolateral membrane is a limiting step in fluid production in exocrine cells and often involves functionally linked Cl(-)/HCO(3)(-) (Ae) and Na(+)/H(+) (Nhe) exchange mechanisms. The dependence of this major Cl(-) uptake pathway on Na(+)/H(+) exchanger expression was examined in the parotid acinar cells of Nhe1(-/-) and Nhe2(-/-) mice, both of which exhibited impaired fluid secretion. No change in Cl(-)/HCO(3)(-) exchanger activity was detected in Nhe2-deficient mice. Conversely, Cl(-)/HCO(3)(-) exchanger activity increased nearly 4-fold in Nhe1-deficient mice, despite only minimal or any change in mRNA and protein levels of the anion exchanger Ae2. Acetazolamide completely blocked the increase in Cl(-)/HCO(3)(-) exchanger activity in Nhe1-null mice suggesting that increased anion exchange required carbonic anhydrase activity. Indeed, the parotid glands of Nhe1(-/-) mice expressed higher levels of carbonic anhydrase 2 (Car2) polypeptide. Moreover, the enhanced Cl(-)/HCO(3)(-) exchange activity was accompanied by an increased abundance of Car2.Ae2 complexes in the parotid plasma membranes of Nhe1(-/-) mice. Anion exchanger activity was also significantly reduced in Car2-deficient mice, consistent with an important role of a putative Car2.Ae2 HCO(3)(-) transport metabolon in parotid exocrine cell function. Increased abundance of this HCO(3)(-) transport metabolon is likely one of the multiple compensatory changes in the exocrine parotid gland of Nhe1(-/-) mice that together attenuate the severity of in vivo electrolyte and acid-base balance perturbations. 相似文献