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Biomedical subjects

H Degani

Publications and source records attributed to H Degani.

83 records · Page 5Linked to original sources

Kinetics of monensin complexation with sodium ions by 23NaNMR spectroscopy.

The kinetics of the sodium binding to the ionophore monensin (Mon) in methanol has been studied by 23NaNMR spectroscopy. Fast quadrupole relaxation of the bound sodium affected the relaxation rate of the free sodium through an exchange process between these two species. The exchange was found to be dominated by the reaction: Na+ + Mon-in equilibrium MonNa. The dissociation rate constant at 25 degrees C is 63 s(-1), with an activation enthalpy of 10.3 kcal/mol and activation centropy of -15.8 cal/mol deg. These results indicate that the specificity of the binding of sodium ions to monensin is reflectied in the relatively slow dissociation process. The entropy changes indicate that the activated monensin-sodium complex undergoes a conformational change, but the existence of a conformational change in monensin anion prior to complexation is excluded.

Chemical Phenomena↗

Ion binding by X-537A. Equilibrium and rate of complexation of Co(2+) in methanol.

The reaction of X-537A (XH) with Co(2+) in methanol to form the complex CoX(+) has been studied fluorometrically to determine the equilibrium constant as a function of temperature. The effect of complexation on the proton NMR spectrum of the X-537A was studied to determine the kinetics of complex formation. Comparing the data for the reaction XM(+) leads to X(-) + M(2+) in methanol at 25 degrees for several M(2+) we find that the equilibrium constants increase in the order CoX(+) less than MnX(+) and span only a factor of 5 while the rate constants increase in the order NiX(+) less than CoX(+) less than MnX(+) and span a factor of more than 100.

Anti-Bacterial Agents↗

Ion binding by X-537A. Rates of complexation of Ni2+ and Mn2+ in methanol.

The rates of complexation are studied through the effects of the paramagnetic ions upon the magnetic resonances of three of the proton species in X-537A = XH. For the dissociation of the complex MX+ leads to M2+ + X- at 25 degrees the rate is (2.4 plus or minus 0.4) x 10(2) sec-1 for Ni2+ and in the range from 2 x 10(4) to 1 x 10(6) sec-1 for Mn2+. For the Ni2+ complex the activation parameters are also determined and discussed in terms of the details of the process. The difference in rate constants found here is much greater than the difference in the dissociation constants.

Anti-Bacterial Agents↗

Correlation of MR imaging and histologic findings in mouse melanoma.

M2R melanoma tumors in male C57 black mice were used to correlate magnetic resonance (MR) images with the corresponding histologic slices and to determine if analysis of the achievable correlation can provide a basis for predicting gross histologic features with MR imaging alone. The MR imaging sections obtained at 4.7 T were each 680 microns thick, with an in-plane resolution of 195 microns. The distribution of melanin within the histologic slices correlated well with the high-signal-intensity regions on the T1-weighted images (T1WIs), while these regions had low signal intensity on the T2-weighted images (T2WIs), providing evidence that melanin or melanin-associated paramagnetic species are responsible for the observed proton relaxation rate enhancement. Viable melanoma cells typically showed intermediate signal intensity on T2WIs, T1WIs, and proton-density images. Necrosis typically had high signal intensity on T2WIs, T1WIs, and proton-density images. Quantitation of the MR imaging results, followed by statistical analysis, demonstrated statistically significant differences between melanin-rich, viable-melanoma, and necrotic regions on MR images.

Animals↗

Angiogenic response of MCF7 human breast cancer to hormonal treatment: assessment by dynamic GdDTPA-enhanced MRI at high spatial resolution.

Dynamic gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI was followed during growth and regression of MCF7 human breast tumors implanted in nude mice in the presence of estrogen and tamoxifen, respectively. Gradient-echo and spin-echo sequences were applied at a temporal resolution of 12 and 100 seconds, respectively, and a spatial resolution of 195 x 390 x 1000 microns. Maps of initial rates of contrast enhancement demonstrated stimulation of local growth of permeable microcapillaries at regions bordering necrotic areas, resulting from tamoxifen treatment. This localized angiogenic stimulation was confirmed by immunohistochemical staining of endothelial cells. After 1 week of tamoxifen treatment, the fraction of tumor pixels exhibiting rapid initial rate of contrast enhancement increased significantly from .28 +/- .05 to .46 +/- .06. In parallel, the fraction of tumor area showing contrast enhancement 3 minutes after Gd-DTPA injection also increased significantly, from .42 +/- .06 to .58 +/- .06. On the basis of these changes, it was possible to assess the response to tamoxifen therapy at an early stage.

Analysis of Variance↗

High resolution MRI of MCF7 human breast tumors: complemented use of iron oxide microspheres and Gd-DTPA.

The differential capacity of iron oxide microspheres and of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) to serve as contrast agents that can map the microcirculation of MCF7 human breast cancer implanted in nude mice has been examined by high resolution MRI. Modulation of signal intensity in T2*-weighted, gradient-echo images after iron oxide administration and the temporal signal enhancement after Gd-DTPA administration were monitored and analyzed at a spatial resolution of 98 x 98 x 500 microm and 195 x 390 x 1,000 microm, respectively. The pathophysiologic features revealed in the contrast-enhanced images were analyzed in reference to those obtained from the corresponding high resolution T2-weighted, spin-echo images and from histologic sections stained with hematoxylin and eosin and with an endothelial cell marker. The results showed that iron oxide microspheres can aid in the characterization of gross histopathologic features and in the assessment of the distribution of the microvasculature, whereas Gd-DTPA estimates the permeability of the microvessels to this agent and determines the cellularity (cell volume fraction) in the vicinity of the vessels.

Animals↗

Kinetics of choline transport and phosphorylation in human breast cancer cells; NMR application of the zero trans method.

The mechanism and kinetics of choline transport and phosphorylation in MCF7 human breast cancer cells was studied by 31P, 13C and 2H NMR, applying the zero trans method. Choline was transported by a Michaelis-Menten like mechanism with a maximum transport rate T(max) = 13.5 +/- 2.6 nmol/hour/mg protein (3.06 +/- 0.6 fmol/cell/hour) and choline concentration at half maximal transport rate of Kt = 46.5 +/- 2.8 microM. The rate of choline phosphorylation was more than two orders of magnitude faster than the rate of its transport (T(max)) maintaining the ratio [phosphocholine]/[choline] higher than 100. The results demonstrated enhanced choline transport and choline kinase activity in breast cancer cells.

Biological Transport↗

Variations in energy and phospholipid metabolism in normal and cancer human mammary epithelial cells.

By comparing the metabolism of human mammary epithelial cells and human breast cancer cells (MCF7 and T47D), proliferating at approximately the same rate, it was possible to isolate the effect of malignancy alone on the energetics and phospholipid metabolism of cancer cells. 31p NMR of perfused mammary cells and of water soluble extracts of these cells showed that the levels of phosphocholine, phosphoethanolamine, and glycerol derivatives of these metabolites were very low and significantly less than that in the cancer cells, suggesting an association of malignancy with induction of phospholipid biosynthesis and breakdown. The level of the high energy phosphates and the rates of glucose consumption and aerobic glycolysis did not reveal distinct differences between normal and cancer cells. The comparable energetic appear to be related to the similarity of proliferating capacity in culture of the normal and cancer cells.

Breast↗