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Biomedical subjects

D M Freeman

Publications and source records attributed to D M Freeman.

34 records · Page 2Linked to original sources
PubMed1990

Lymphocyte metabolism and cytotoxic activity monitored with 31P magnetic resonance spectroscopy.

Continuous metabolic monitoring of human lymphocytes and a tumor cell line was achieved by means of nuclear magnetic resonance (NMR) applied to cells suspended in alginate gels. Human peripheral blood lymphocytes cultured in vitro were examined with 31P magnetic resonance spectroscopy (MRS) before and after activation with phytohemagglutinin and interleukin-2 (IL-2). Following the addition of these biological response modifiers, increases in [ATP], phosphomonoesters (PME), and phosphodiesters occurred. These appear to be markers of lymphocyte stimulation. Lymphocyte pH was unchanged. A target tumor cell line (K562) showed 31P NMR spectra that differed significantly from that of lymphocytes. When lymphocytes were mixed with tumor cells (to induce tumor cell death), and monitored by 31P MRS, levels of inorganic phosphate (Pi) increased, [PME] levels fell, and release of H+ was inhibited. 31P MRS may therefore provide a noninvasive assay of lymphocyte-mediated tumor cell killing that will have application in monitoring treatment in patients undergoing this type of therapy.

Adenosine Triphosphate↗
PubMed1989

Metabolite specific proton magnetic resonance imaging.

An imaging method is described that makes use of proton double quantum nuclear magnetic resonance (NMR) to construct images based on selected metabolites such as lactic acid. The optimization of the method is illustrated in vitro, followed by in vivo determination of lactic acid distribution in a solid tumor model. Water suppression and editing of lipid signals are such that two-dimensional spectra of lactic acid may be obtained from a radiation-induced fibrosarcoma (RIF-1) tumor in under 1 min and lactic acid images from the same tumor in under 1 hr at 2.0 T. This technique provides a fast and reproducible method at moderate magnetic field strength for mapping biologically relevant metabolites.

Animals↗
PubMed1989

Differentiation between renal cortex and medulla in the response to hypotension using localized 31P magnetic resonance spectroscopy.

Experiments were designed to test the hypothesis that renal medulla is more sensitive to hypoxia than is the cortex. Using the one-dimensional phase encoding technique to perform 31phosphorus magnetic resonance spectroscopy in a perfused porcine kidney preparation, cortex and medulla were differentiated on the basis of the unique resonance at 3 ppm found only in medulla. Hypotension-induced hypoxia reduced total renal oxygen consumption by 60%, and urine flow by 44%. Nonlocalized 31P MRS spectra showed that [ATP]/[Pi] ratio fell by 40%, and intrarenal pH by 0.1 unit. Virtually all of these changes could be accounted for by changes in the renal cortex, where initial [ATP]/[Pi] was higher than in medulla (1.16 vs. 0.68). In medulla [ATP]/[Pi] fell only 29% (n.s. versus control) and pH remained unchanged during hypotension. Thus the cortex appears to be more sensitive to hypoxia in this preparation, and observations fail to support the proposed hypothesis. They are consistent, however, with the greater capacity of medulla for anaerobic glycolysis. Localized 31P MRS provides improved noninvasive metabolic assessment of cold-preserved kidneys.

Adenosine Triphosphate↗
PubMed1988

The role of fluid inertia in mechanical stimulation of hair cells.

Hair cells, which are the receptor cells of hearing and equilibrium in vertebrates, produce electrical responses when their hair bundles are displaced by sensory stimuli. This paper summarizes the results of a theoretical study of the fluid mechanics of hair-bundle motion. The principal conclusion is that fluid inertia, which has not been included in previous studies, plays a critical role in the mechanics of hair bundles and, hence, in the processes of sensory reception in hair-cell organs.

Animals↗
PubMed1986

Magnetic resonance spectroscopy for the determination of renal metabolic rate in vivo.

The method of magnetic resonance spectroscopy has been validated and applied to the determination of renal metabolic rate in vivo. Using an indwelling detector coil, 31P NMR spectra from one kidney of anesthetized rats were quantified. The concentration of ATP was the same as that determined enzymatically, but both ADP and Pi were substantially lower. Only 25% of renal Pi and virtually none of the ADP were detected by NMR. The remainder is assumed to be bound to proteins. These concentrations of metabolites contributed to a significantly increased phosphorylation potential, which in turn should increase the free energy of hydrolysis of ATP. Saturation transfer, a non-destructive magnetic technique for the measurement of chemical exchange, was readily able to detect synthesis of ATP from ADP and inorganic phosphate. The rate of ATP synthesis determined was comparable to that determined in parallel studies of renal oxygen consumption. An ATP:O ratio of approximately 2 was found, indicating that fatty acid is the preferred fuel of respiration of the rat kidney in vivo.

Adenosine Diphosphate↗
PubMed1977

The immunizing effect of influenza A/New Jersey/76 (Hsw1N1) virus vaccine administered intradermally and intramuscularly to adults.

2The immunogenicity and reactogenicity of inactivated influenza A/New Jersey/76 (Hsw1N1) whole-virus vaccine administered intradermally (40 chick cell-agglutinating units/0.1-ml dose) and intramuscularly (im; 200 chick cell-agglutinating units/0.5-ml dose) to human adults were evaluated. Among 18-24-year-old persons initially free of detectable antibody, intradermal vaccination induced lower titers of hemagglutination-inhibiting antibodies than did im vaccination, and a sequence of intradermal and im vaccinations did not offer any serologic advantage over one im dose. In contrast, persons over the age of 24 who initially lacked detectable antibody had as good a serologic response to intradermal vaccination as to im vaccination. Among individuals who had antibody before vaccination, immunization by either route induced greater increases in titers of hemagglutination-inhibiting antibody than occurred in initially antibody-negative persons, even when the latter were given two doses of vaccine. Somewhat fewer systemic reactions occurred after intradermal than after im vaccination, but the intradermal route was associated with local reactions in almost all vaccinees and with some residual pigmentary changes. These results suggest that intradermal vaccination should be used only in very selected circumstances.

Adolescent↗
PubMedDate not supplied

Early metabolic effects of hypotension on rat kidney.

Saturation-transfer phosphorus nuclear magnetic resonance (STNMR) has been applied to the rat kidney in vivo. The rate of renal metabolism determined by this method compares favorably with the renal oxygen consumption, assuming an ATP:oxygen ratio of 2. Hemorrhagic hypotension resulted in a 20% fall in renal blood flow and a significant fall in oxygen consumption. The rate of renal metabolism fell by 50%. This rate of ATP synthesis was below that required to maintain a normal [ATP], but renal [Pi] was not increased. When renal perfusion was reduced by 60%, intrarenal [Pi] rose. When [P1] was elevated, the method os STNMR no longer gave a reliable measure of the rate ATP synthesis, indicating that this new Pi pool was not in rapid chemical exchange with ATP. STNMR represents a useful noninvasive means of monitoring renal metabolic rate, with limitations due to insensitivity and the existence of multiple pools of intrarenal Pi.

Adenosine Diphosphate↗