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J C Lyons

Publications and source records attributed to J C Lyons.

26 records · Page 2Linked to original sources

Effects of amiloride on intracellular pH and thermosensitivity.

Amiloride, a diuretic drug, is a potent inhibitor of Na+/H+ exchange through the plasma membrane, and has been reported to enhance thermal damage in tumor cells in vitro. We investigated the possible relationship between changes in the thermal response of SCK mouse mammary tumor cells in vitro and changes in intracellular pH (pHi) due to amiloride in the present study. At a concentration of 0.5 mM, amiloride reduced the shoulder (Dq) without causing significant change in the slope (Do) of the survival curve of SCK cells heated once at 43 degrees C. On the other hand, 0.5 mM of amiloride sensitized thermotolerant cells to heat as shown by a reduction in Do. The presence of amiloride during the interval between the first and second heatings slightly reduced or inhibited the development of thermotolerance. The pHi was measured with the BCECF fluorescence method. The presence of 0.5 mM amiloride significantly reduced pHi in both pH 7.2 and 6.6 medium. Heating the SCK cells at 43 degrees C in pH 7.2 or 6.6 medium also reduced the pHi. The combined effect of heat and amiloride in reducing the pHi of SCK cells was additive. These results suggest that the effects of amiloride on the thermal response of SCK cells might be mediated in part by a decrease in pHi. The possibility that the effects of amiloride on the thermal response of tumor cells are mediated by other biochemical changes, such as inhibition of protein synthesis, however, could not be ruled out.

Amiloride↗

Evaluation of radiographic findings in painful hip arthroplasties.

A retrospective study of 50 surgically confirmed painful hip arthroplasties was performed to identify the roentgenographic findings that are most important in the detection of component loosening or infection. Plain film radiographs and subtraction arthrograms were reviewed in all cases, and specific features revealed by these two radiographic modalities indicative of component failure were identified. Seventeen patients had radioisotope bone scans and 13 of these had additional gallium scans. Plain film roentgenograms correctly identified loosening in 69% of acetabular and 84% of femoral components. Subtraction arthrography had an accuracy of 96% for both acetabular and femoral component loosening. Scintigraphic studies were correct in 77% of acetabular and 89% of femoral components; gallium scans identified 77% of infected hip prostheses.

Adult↗

The snapping iliopsoas tendon.

Herein we describe a previously seldom recognized variety of snapping hip, which is caused by snapping of the iliopsoas tendon over the iliopectineal eminence when the femur is moved from the flexed position at the hip and extended through 45 degrees of flexion. The finding is demonstrated with the patient supine and gently resisting gravity with the iliopsoas muscle, thus placing it under tension. At approximately 45 degrees of flexion, the iliopsoas tendon in two patients was confirmed radiographically to snap abruptly, coincident with an audible sound over the iliopectineal eminence of the pelvis. We believe that this occurs relatively frequently and is generally asymptomatic.

Adult↗

Stabilization of aluminum hydroxide gel by specifically adsorbed carbonate.

Ion-free aluminum hydroxide gel, prepared by the hydrolysis of aluminum tri-sec-butoxide, was observed by IR, X-ray analysis, and pH-stat titration to undergo rapid structural changes leading to the formation of pseudoboehmite and bayerite. The rate of development of order was directly related to the water-aluminum molar ratio. The Al--O bands at 625 and 470 cm-1 were the most sensitive indicators of the development of order in the gel structure. Direct evidence for the stabilizing effect of specifically adsorbed carbonate was obtained when carbon dioxide was introduced during the hydrolysis of aluminum tri-sec-butoxide. The resulting aluminum hydroxycarbonate gel possessed excellent antacid properties, retained its amorphous nature upon aging, and contained no cations other than aluminum. Hydrolysis of aluminum tri-sec-butoxide in the presence of stoichiometric amounts of sodium bicarbonate resulted in the immediate formation of crystalline sodium aluminum hydroxycarbonate (dawsonite).

Adsorption↗

Gaucher's disease and glioblastoma multiforme in two siblings: a clinicopathologic study.

The clinical and pathologic features of two brothers with the adult form of Gaucher's disease, both of whom developed cerebral glioblastoma multiforme, are presented. Neither patient had a long-standing neurologic disorder, and morphologic evidence of nervous system glucocerebroside storage was not seen. Despite the known increased incidence of malignancy in Gaucher's disease, a review of the literature and of sixty-two Mayo Clinic cases of adult onset Gaucher's disease revealed only one other instance of the association with glioma. The significance of the relationship is unknown.

Brain Neoplasms↗

Use of arsenic trioxide as an antivascular and thermosensitizing agent in solid tumors.

Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.

Angiogenesis Inhibitors↗

Effect of acidic environment and p53 on apoptosis induction by hyperthermia.

The effect of environmental acidity on the induction of apoptosis by heat was investigated. Human colorectal tumour RKO.C cells, carrying wild-type p53 and isogenic RC10.1 cells deficient in p53, were heated at 42.0 degrees C for 1 h in pH 7.5 or pH 6.6 medium and the apoptosis was assessed based on the flow cytometic determination of DNA content, DNA fragmentation, and PARP cleavage. The degree of apoptosis after heating in pH6.6 medium was greater than that in pH 7.5 medium in both RKO.C cells and RC10.1 cells. When heated in the same pH medium, more apoptosis occurred in the RC10.1 cells than in the RKO.C cells. Heating increased the expression of p53 protein and p21 protein markedly in RKO.C cells and slightly in RC10.1 cells. Expression of these proteins was slightly greater in pH 7.5 medium than in pH 6.6 medium. The expressions of Bax protein and Bcl-2 protein, which are known to control apoptosis, were not altered by heating. It was concluded that an acidic environment enhances heat-induced apoptosis. It was also concluded that heat-induced apoptosis is lessened by p53 and that Bcl-2 and Bax are not involved in the induction of apoptosis by hyperthermia.

Apoptosis↗

A differential low pH effect on tumour cells grown in vivo and in vitro when treated with hyperthermia.

The effectiveness of low extracellular pH in sensitizing cells to heat was studied using SCK mammary carcinoma cells of A/J mice. Solid tumours of 400-600 mg or cells grown in vitro for less than 13 weeks were dispersed to single cells and the in vivo- or in vitro-derived cells were suspended in a medium of pH 7.2 or 5.5-6.6 and then heated at 41-44 degrees C in vitro using a water bath. The dispersion procedure did not alter the heat sensitivity of these cells, but acidic medium of pH below 6.6 caused an increase in heat sensitivity. This effect of low pH decreased with increasing temperature of heating for both cell types. However, the effect was much smaller on in vivo-derived cells than that on in vitro-derived cells for any heating temperature tested. This reduction of the pH effect was also observed for cells derived from larger tumours as well as tumours at an early stage of growth in which the internal milieu was not acidic. This indicates that cellular adaptation to low intratumour pH was not the cause of the reduced pH effect; instead, factors other than low pH must cause the reduced pH effect seen in tumour-derived cells.

Animals↗