Biomedical subjects

C J Swallow

Publications and source records attributed to C J Swallow.

21 records · Page 2Linked to original sources

PubMed1989

Mechanisms of cytoplasmic pH recovery in acid-loaded macrophages.

In the acidic microenvironment of an abscess, efficient antimicrobial function is dependent upon the phagocyte's maintenance of its physiological intracellular pH. To determine the mechanisms by which macrophages recover from an intracellular acid load, the cytoplasmic pH of murine peritoneal macrophages was measured using the pH-sensitive cytoplasmic fluorescent dye bis(carboxyethyl)-5(6)-carboxyfluorescein. These studies showed that pH recovery was primarily mediated by a Na+/H+ antiport in the plasma membrane which exchanged intracellular H+ for extracellular Na+. The proportion of pH recovery mediated by this exchanger was determined by measuring the rate of acid extrusion in the presence of the Na+/H+ antiport inhibitor, amiloride. Mean rate of acid extrusion (in mM/min) was reduced from 4.4 +/- 0.2 in control cells to 1.6 +/- 0.2 in the presence of amiloride (mean +/- SEM, n = 8, P less than 0.01), demonstrating the presence of a second mechanism for pHi recovery. Inhibition of this residual recovery both by the sulhydryl reagent N-ethylmaleimide and by ATP depletion suggested that the additional mechanism was an ATP-dependent proton extrusion pump. Thus, macrophages have at least two efficient mechanisms for maintaining physiological pH when exposed to an intracellular acid load. Since the Na+/H+ antiport is inhibited at low extracellular pH, the maintenance of physiological cytoplasmic pH, and of normal cell function, within the acidic milieu of a tumor or abscess may depend on the alternate mechanism of pH recovery demonstrated here.

Acids↗

PubMed1988

Cytoplasmic pH regulation in macrophages by an ATP-dependent and N,N'-dicyclohexylcarbodiimide-sensitive mechanism. Possible involvement of a plasma membrane proton pump.

Cytoplasmic pH (pHi) regulation was studied in thioglycolate-elicited murine macrophages using fluorescent probes. Acid-loaded macrophages regained normal pHi by extrusion of H+ equivalents across the plasma membrane. A fraction of this recovery was due to Na+/H+ exchange, as evidenced by its partial Na+ dependence and amiloride sensitivity. The residual, Na+-independent pHi recovery (approximately 50% of the total) persisted in the nominal absence of HCO3- and was insensitive to disulfonic stilbenes, ruling out mediation by anion exchange. In contrast, intracellular alkalinization and H+ extrusion from the cells were inhibited by N-ethylmaleimide, by N,N'-dicyclohexylcarbodiimide or by prior depletion of intracellular ATP. These observations are consistent with the existence of a H+-pumping ATPase in the plasma membrane of macrophages. The mechanism of activation of the ATP-dependent H+ extrusion process was also investigated. In other systems, Ca2+ mobilization has been suggested to signal an exocytic insertion of H+ pumps into the plasma membrane. Acid loading of macrophages was accompanied by an elevation of the cytosolic Ca2+ concentration ([Ca2+]i), measured using indo-1. These results are consistent with a role for Ca2+ mobilization in the activation of H+ extrusion.

Adenosine Triphosphate↗

PubMedDate not supplied

Malignant gastrointestinal stromal tumors of the small intestine: a review of 50 cases from a prospective database.

BACKGROUND: Malignant gastrointestinal stromal tumors (M-GIST) are rare mesenchymal tumors originating in the wall of the gastrointestinal (GI) tract. Previous studies have included limited numbers of patients, and most included malignant and benign cases from throughout the GI tract. We reviewed the experience of a single tertiary cancer care center with M-GIST of the small intestine only. METHODS: A prospective database identified all patients seen from 1989 to 1998. Clinical and pathological data, treatment, and outcome were analyzed. Overall median follow-up time was 24 months (range, 1-176 months). RESULTS: Fifty patients (31 male, 19 female) were identified. Mean age at diagnosis was 55 years. Disease was localized in 11 patients, locally advanced (invasion into adjacent organs/peritoneum) in 24 patients, perforated in 4 patients, multiple primary lesions in 2 patients, and distant metastases in 9 patients. All patients underwent resection, which was complete in 70%. Locoregional recurrence (LR) developed in 43% (median, 25 months), and distant metastases in 59% (median, 21 months) of patients at risk. At last follow-up, 14 patients were alive (6 disease-free), 2 had died disease-free, and 34 died with recurrent disease. Overall survival (OS) was similar for localized and locally advanced disease; OS also was similar for patients with multiple primaries and distant metastases at diagnosis. Patients were grouped into three stages: (I) patients with localized and locally advanced disease; (II) patients with perforated; and (III) patients with multiple primaries and distant metastases. Actuarial OS at 5 years was 41% (n = 50)--42% for those with complete resection and 8% for incomplete resection. Univariable analysis showed that earlier stage at diagnosis (P = .001) and completeness of resection (P = .004) predicted for longer OS. CONCLUSIONS: Most patients with M-GIST of the small intestine relapse following resection, but survival may be prolonged. In univariable analysis, stage at presentation and complete resection were significant prognostic variables for OS; grade was not significant. Localized and locally advanced M-GIST of the small intestine have a mean OS > 5 years. Complete resection should be the goal of initial surgical treatment.

Adult↗