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Biomedical subjects

I S Longmuir

Publications and source records attributed to I S Longmuir.

At least 19 recordsLinked to original sources
PubMed1992

Changes in tissue histology associated with adaptation and acclimation to hypoxia.

Newborn kittens are adapted to hypoxia by having an oxygen department respiration rate. In part, this is due to the structure of the liver which results in a great reduction of oxygen consumption in this organ in response to hypoxia. Older animals possess an oxygen independent respiration rate which is not lost when they acclimate to hypoxia. Instead, there are histological changes which permit the liver to consume oxygen at the same rate as before by facilitating intracellular oxygen transport.

Acclimatization↗
PubMed1990

Hyperchylomicronemia, oxygen affinity and proton passage across the red cell membrane.

Previously we have shown that HC alters significantly the affinity of hemoglobin for oxygen. This evidence stands in support of earlier investigations presented by Ditzel and Dyerburg (1977). Exposure to 6% chylomicra, slowly produced a decrease in the pO2 of human blood (37 degrees C, at in vivo pH) amounting to a 6.0 mm Hg leftward shift in the P-50. This increase in oxygen affinity may be due to the Bohr shift since exposure to HC produced an increase in intracellular pH by abolishing the proton gradient across the red cell membrane. We postulate that exposure to HC might physically modify the composition of the red cell membrane so that proton passage is permitted and the intracellular pH rises to approximate that of the extracellular pH. An oxidative phosphorylation uncoupling agent (CCCP), abolishes the proton gradient and produces an immediate decrease in the pO2 similar to that produced by HC. We explored the suggestion that proton passage might be facilitated by an increase in the membrane fluidity produced by a decrease in membrane cholesterol. However no decrease in red cell membrane cholesterol was found on exposure to 6% chylomicra. Although the molecular mechanism remains unclear, this event would dramatically reduce oxygen delivery to the myocardium and might prove to be an important factor in the incidence of myocardial hypoxia.

Carbonyl Cyanide m-Chlorophenyl Hydrazone↗
PubMed1989

The effect of hyperchylomicronaemia on oxygen affinity in human blood.

Evidence for a leftward shift of the oxygen dissociation curve in HC patients was first described by Ditzel and Dyerberg. These results were challenged by Robertson et al., who saw no shift using a different technique to obtain P-50. Both methods are open to possible errors. In order to clarify the mechanism whereby HC blood shows an increased affinity for O2, the method of Longmuir and Chow was used since it is unaffected by these problems. Exposure of blood to various lipid emulsions was shown to exhibit a slow fall in pO2 due to increased binding of oxygen to haemoglobin. During the same period the pH difference across the cell membrane is largely abolished. As a result the oxygen dissociation curve is displaced to the left by the Bohr shift. This is an acute and dramatic event. We postulate that this increased affinity of red blood cells for O2 may predispose patients in the HC state to myocardial ischaemia by this mechanism.

Chylomicrons↗
PubMed1988

Liver organelle changes on exposure to hypoxia.

Exposure of mice to hypoxia reduces the length of each element of endoplasmic reticulum. This may shorten the path length of oxygen within the cell and have an adaptive advantage. There were no significant changes in the other organelles.

Animals↗
PubMed1988

Control of non-respiratory metabolism by tissue oxygen.

Many intracellular enzymes are activated or inactivated by S-thiolation. The extent of this depends on the local oxygen tension. Thus oxygen should not be considered as an enzyme poison for certain enzymes but as a regulatory of metabolic activity.

Animals↗
PubMed1987

Adaptation to hypoxia.

Many biochemical changes occur during acclimation to altitude. Some appear to be deleterious, but the increase in cytochrome-P 450 and the changes in the endoplasmic reticulum seem to be beneficial. The latter changes could reduce the capillary to oxidase gradient to compensate for the lower capillary oxygen tensions. The possibility of accelerating acclimation to hypoxia by using drugs which produce similar changes is being explored.

Acclimatization↗
PubMed1986

Influence of PaO2 on cerebral macro- and microcirculation as observed by light reflection: time course of changes.

A silicon intensified target camera was used to study cerebral cortical vessels of the cat through a skull window implant, and red cell content changes were measured by light reflectance. Red cell content changes were observed in cerebral arterioles, capillaries, and venules when the PaO2 was decreased by lowering the PiO2. The time course of change in the diameter of the arterioles and venules was measured by selecting a cross section of the vessel plus some surrounding tissue. From the averaged cross-sectional reflectance signal, the change in vessel diameter was followed as a function of time following the PiO2 change. All vessels of greater than 10 microns were observed in focus. Substantial areas where no vessels could be discriminated would contain only capillaries, and changes in light reflectance from such areas would indicate changes in capillary red cell content. The time course of these changes following a step decrease in PiO2 was recorded. Results show that the sequence of red cell content increase in cerebral microcirculation during hypoxia is capillary before venule and arteriole. The times of initial red cell content increase are 37.9 +/- 7 s, 59.7 +/- 7.9 s, and 60.8 +/- 9.1 s, respectively. These results suggest an increase in the capillary bed red cell content as the initial response to hypoxia, but venules and arterioles change only on longer exposure to hypoxia. The sequence of the increase in red cell content suggests the capillaries rather than the arterioles are the vessels which respond to the oxygen autoregulation signal.

Animals↗
PubMed1984

Synthesis of cytochrome P-450 in isolated liver cells during exposure to hyperoxia.

Mouse hepatocytes were separated within 15 min of the death of the animal. A method of determining cytochrome P-450 was developed and used to show that cells prepared quickly still contained normal levels of this pigment. Cells suspended in complete culture medium were exposed to various partial pressures of oxygen for 30 min. When exposed to anoxia there was a 30% loss of cytochrome; at 30-50 Torr, a 30% increase; to 150 Torr, a 10% decrease; and to 700 Torr or higher, 30%-60% increase. The time course of the increase, at those tensions at which it was obtained, showed the increase occurred for 1 to 2 h and was followed by a continual loss. This final loss was at approximately the same rate at all tensions, whether or not there was an initial rise. Thus the cytochrome P-450 levels of isolated hepatocytes show qualitatively the same response to varying oxygen tensions that they do in intact animals.

Animals↗
PubMed1981

Use of an encapsulated fluorescent probe to measure intracellular PO2.

The objectives of this investigation were to produce a reliable, sensitive probe to measure intracellular PO2 with a high degree of resolution and to apply this technique to biological systems. A fluorescent molecule, pyrene dissolved in paraffin oil, was encapsulated in polyacrylamide to form a probe of nanometer dimensions. The quantitative and microscopic oxygen values were determined by analyzing the quenching of the fluorescence of the probe by oxygen, as displayed on a television monitor by a silicon-intensified-target camera. The nanocapsules had a sensitivity of approximately 1 mm PO2, a spatial resolution of 0.5 micrometer, and a temporal resolution of milliseconds. Calibrated nanocapsules within nonrespiring Amoeba proteus responded to ambient partial pressures of oxygen. At two different ambient partial pressures, nanocapsules engulfed by respiring amoebas indicated an intracellular PO2 28 mm Hg less than extracellular PO2. The capsules retained their sensitivity to oxygen for at least 8 months.

Amoeba↗
PubMed1980

Intracellular oxygen measurements of mouse liver cells using quantitative fluorescence video microscopy.

Our currently developed fluorescence video microscope can measure fluorescence intensities with an error of +/- 1.5% of full scale in 65536 different positions of a microscope field. With a video frame freeze acquisition time of 33 ms, time-dependent changes of this order of time or slower can be followed. Using cells which have absorbed pyrene-1-butyrate to an intracellular concentration of 0.05 to 1 mM, the changes in fluorescence intensity with oxygen concentration are easily measured. The spatial resolution for data collection is 0.5 micron when a 54X objective is used. The individual Stern-Volmer quenching constants of each individual pixel were measured for agar slices and mouse liver cells treated with pyrenebutyric acid. The distribution of quenching constants for agar follows a normal curve about a mean value of 16 . 10(-4) torr-1. The data for mouse liver cells gave a non-normal distribution of quenching constants with a mean value of 18 . 10(-4) torr-1. The greater spread of the data from cells is interpreted as evidence for a real biological variation in the solubility coefficient of oxygen in different locations within the cell. In all the cells examined, this distribution has been observed to be non-random and appears to be associated with specific cell structures.

Animals↗
PubMed1980

In vivo and in vitro induction of cytochrome P-450 synthesis in hyperoxia.

Exposure of dark- or light-adapted mice to 1--3 ATA oxygen for times ranging from 15 min to 4 h caused a progressive increase in P-450, which peaked and then decayed. The rate of decay appears to be independent of PO2. A linear, inverse relationship was noted between the PO2 in the range of 1--4 ATA and the duration of exposure needed to obtain maximum P-450 levels. Cytochrome P-450 was induced by hyperoxia in vitro in a suspension of hepatocytes, and this induction was prevented by inhibitors of transcription and translation and by disulfiram. Cytochrome P-450 induction is not a general phenomenon of stress, albeit physical restraint may decrease the level of P-450 induced. Induction was a specific effect of increased oxygen tensions and was not due to pressure per se. Neither equivalent pressures of compressed air in the in vivo experiments nor equivalent pressures of nitrogen in the in vitro experiments induced P-450. Induction in vivo was inhibited by disulfiram and metyrapone. Hyperoxia is the most rapid inducer of P-450 yet found, and this response may represent a protective mechanism against hyperoxia.

Animals↗