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R J Hitzemann

Publications and source records attributed to R J Hitzemann.

87 records · Page 5Linked to original sources

Effect of ganglioside-GM1 on the order of phosphatidylcholine-cholesterol multilamellar liposomes. A fluorescence polarization study.

The effect(s) of bovine brain ganglioside-GM1 on the order of phosphatidylcholine-cholesterol membranes were studied using steady-state fluorescence polarization (FPZ) techniques with 1,6-diphenyl-1,3,5-hexatriene (DPH) as the membrane probe. In the absence of cholesterol, GM1 (30 mol%) increases both membrane order and the phase transition temperature of dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) membranes. However, in the presence of cholesterol (0.3 or 0.5, cholesterol/phospholipid molar ratio), GM1 significantly decreases steady-state anisotropy (rs) at temperatures above the Tm for the particular phospholipid. This effect may, in part relate to a dilution of membrane cholesterol and is shared by bovine brain sphingomyelin (SM). GM1 (30 mol%) increases the order of 1-palmityl-2-oleyl-PC (POPC) membranes. However, in the presence of cholesterol (0.3 molar ratio) GM1 neither increases or decreases order. Thus, in cholesterol containing artificial membranes, the effect of GM1 depends on the phosphatidylcholine (PC) fatty acid composition and may not be evident from the effect of GM1 on pure PC membranes.

1,2-Dipalmitoylphosphatidylcholine↗

Repeated electroconvulsive shock or chronic morphine treatment increases the number of 3H-D-Ala2,D-Leu5-enkephalin binding sites in rat brain membranes.

Experiments were performed in rats to evaluate the possible mechanisms responsible for the pharmacological cross-sensitization observed between repeated electroconvulsive shock (ECS) and chronic morphine administration. Repeated daily ECS for 9 days as well as chronic morphine pellet implantation resulted in a significant increase in the number of 3H-DADLE binding sites (Bmax values of 231 and 196 fmoles/mg protein, respectively). By contrast, single ECS, repeated sham ECS, and placebo pellet-treated rats all had significantly lower Bmax values (approx. 170 fmoles/mg protein). Affinities were not significantly altered by these treatments (Kd values between 3.1 and 4.0 nM). These data may link pharmacological cross-sensitization (repeated ECS and chronic morphine treatment) with a functional increase in the number of available opioid receptors.

Animals↗

On the physical properties of red cell ghost membranes in the affective disorders and psychoses. A fluorescence polarization study.

Membrane order was measured in the erythrocyte ghost membranes of DSM-III schizophreniform disorder (SF), DSM-III schizophrenic (SCZ) and DSM-III manic (bipolar) (M) patients and a group of age- and sex-matched controls. Fluorescence polarization with the probe 1,6-diphenyl-1,3,5-hexatriene was used to determine the steady-state fluorescence anisotropy (rs). The SF group showed a significant increase in rs (delta rs = 0.037) from the control group. Although the means were not significantly different, 3 of 8 Ms and 5 of 8 SCZs also had rs values greater than the highest control value. Thermotropic behavior of the membranes was evaluated over the range of 40 to 20 degrees C. No difference among groups in membrane enthalpy was detected. Thus, the differences in rs appear to be associated with differences in entropy. Phosphatidylcholine (PC) levels, which were known to be abnormal in these patients, were compared with the rs values. A significant (P less than 0.001, r = -0.63) linear correlation between rs and membrane PC levels was observed. Overall these data further support the view that unusual membrane biophysical factors may occur with high frequency in the psychoses and affective disorders.

Adult↗

Characterization of a GM1-dependent surface interaction for alcohol with DPPC membranes.

A unique surface interaction for perdeuterated ethanol and 1-butanol with dipalmitoylphosphatidylcholine (DPPC)/monosialoganglioside (GM1) multilamellar vesicles can be detected from the fast exchange averaging of the nuclear quadrupole coupling constant of the alcohol in the free and bound states using deuterium NMR. At 1.0% perdeuterated ethanol or 0.5% perdeuterated 1-butanol, a small splitting of the alcohol resonance(s) was detected in the liquid-crystalline phase, but not in the gel phase of the bilayer. The observed splitting is proportional to the fraction of alcohol bound and is dependent on temperature, alcohol, and GM1 concentrations. The splitting was only observed in the presence of negatively charged GM1 but not neutral asialoganglioside (asialo-GM1) in DPPC multilamellar vesicles. The observed splitting decreased with the addition of Ca2+ or Mg2+ ions. This effect was reversed upon the addition of chelating agents. It is proposed that the unique surface interaction for alcohol may result from small surface perturbations of the phosphatidylcholine head groups by the negatively charged sialic moieties of neighboring GM1 molecules in the bilayer.

1,2-Dipalmitoylphosphatidylcholine↗

Prenatal valproic acid exposure decreases neuronal membrane order in rat offspring hippocampus and cortex.

Sprague-Dawley rats were administered 0 or 200 mg/kg of valproic acid (VPA) on days 7-18 of gestation. Controls were pair-fed. On postnatal day 28, analyses of brain tissues were performed on enriched neuronal membrane fractions from cerebellum, hippocampus, and cortex for anisotropy using the membrane probe 1,6-diphenyl-1,3,5-hexatriene (DPH). No significant differences in membrane anisotropy were noted in the cerebellum, but a significant reduction in anisotropy in the hippocampus and cortex was observed. This change corresponds to a 3-5 degrees C increase in temperature or that produced by other membrane disordering agents (ethanol, phenytoin). An association between membrane anisotropy and functional effects of prenatal VPA exposure is discussed.

Animals↗

MR-PET image coregistration for quantitation of striatal dopamine D2 receptors.

PURPOSE: Our goal was to assess the utility of MR-PET image coregistration to quantify dopamine D2 receptors in striatum. METHOD: Twenty-nine normal subjects were investigated with PET and [11C]raclopride and with MRI. D2 receptors were quantified using the ratio of the distribution volume in striatum to that in cerebellum. Measures obtained using regions selected directly from the PET images were compared with those obtained from MR images and then projected to coregistered PET images. RESULTS: There were no differences between measures selected from the PET images (3.9 +/- 0.5) and those from the MR images (3.9 +/- 0.65). The values for these two measures were significantly correlated and corresponded to r = 0.9, p < 0.0001. CONCLUSION: Regions of interest selected directly from PET images, where there is a large contrast between the region of interest and background, as for the case of dopamine D2 ligands, are almost identical to those obtained from coregistered MR images.

Adult↗