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PubMed1983

[Quantitative characteristics of blood redistribution after death by radioactive indication].

The methods of radioactive detection and external radiometry were used to study the distribution of blood in cats and rats during 24 hours after heart arrest. Labeled albumins (131I) and erythrocytes (51Cr) were used as blood indicators. The animals after death were stored in a horizontal or, in some tests, in vertical position at room temperature. The activity was measured in the horizontal and sagittal planes in strictly defined sites (30 altogether) or by scanning of the entire body within 3-5 min after circulation arrest as well as at 5 and 24 hours. No significant changes in distribution of plasma and erythrocytes during 24 hours postmortem in the horizontal position were shown to occur, while in the vertical position there was an insignificant increase of the blood content in the lower part of the body.

Animals↗
PubMedDate not supplied

[A comprehensive radioisotope assessment of the effectiveness of Ferrum Lek in patients with iron-deficiency anemia].

Before and after treatment iron metabolism was evaluated in 37 iron deficient women given intravenous Ferrum Lek. In addition to standard blood counts and serum iron tests, iron metabolism was investigated with Fe-59 whole body radiometry in a low-background camera. The treatment effect was assessed in 1.3 and 6 months. The red blood cells and iron content in the serum returned to normal values. The effect persisted for 6 months. The initial 3 months iron accumulated in the depot, being further distributed in the blood. Total body iron 6 months after the treatment was at the baseline levels. It is thought adequate to use Ferrum Lek in the management of women with iron deficiency anemia.

Adult↗
PubMedDate not supplied

[Drug kinetics in soft contact lenses. I. In vitro studies].

The in vitro kinetics (specifically, absorption and desorption) of drugs belonging to various pharmacological groups (atropine sulfate, gentamicin sulfate, dexamethasone, lecozyme, and poludan) in soft contact lenses (low-hydrophilic with 40% aqueous content and highly hydrophilic with 74% aqueous content. 0.2 and 0.7 mm thick) was studied by radiometry, as were the effects of chemical structure of a drug, hydrophilic properties and thickness of soft contact lenses, and temperature of solution on these processes.

Anti-Bacterial Agents↗
PubMed1998

Quantitative comparison of autoradioluminographic and radiometric tissue distribution studies using carbon-14 labeled xenobiotics.

The tissue distribution of two 14C drugs were quantitatively compared using the techniques of whole body autoradioluminography (WBAL) and radiometry. Quantitative analysis of tissue radioactivity in whole body cryosections was accomplished from storage phosphor images using the MicroComputer Imaging Device. After obtaining whole body sections from four frozen rats and three frozen ferrets, each WBAL-sectioned specimen was partially thawed before obtaining tissue samples for radiometric analysis. For all tissues examined, concentrations of radioactivity determined by WBAL were comparable with those determined by dissection and liquid scintillation analysis (DLSA), except for renal tissue obtained from different kidneys of the same ferret and for rat ocular tissues. A 2-fold difference was observed between WBAL and DLSA evaluations of radioactivity in the contralateral kidneys of one ferret. DLSA evaluation only provided an assessment of total radioactivity in the eye, whereas WBAL evaluation determined the selective distribution of radioactivity to ocular tissues. Resolution in DLSA evaluation of ocular tissues was restricted by limitations of the dissection procedure. These results indicated that the quantitation of tissue radioactivity by WBAL was as precise as DLSA evaluation, and WBAL also provided results to the quantitative distribution of radioactivity to localized sites in organs not feasible by DLSA.

Administration, Oral↗
PubMed2000

Optical and thermal properties of nasal septal cartilage.

BACKGROUNDS AND OBJECTIVES: The aim of the study was to measure the spectral dependence of optical absorption and reduced scattering coefficients and thermal conductivity and diffusivity of porcine nasal septal cartilage. Values of optical and thermal properties determined in this study may aid in determining laser dosimetry and allow selection of an optical source wavelength for noninvasive diagnostics for laser-assisted reshaping of cartilage. MATERIALS AND METHODS: The diffuse reflectance and transmittance of ex vivo porcine nasal septal cartilage were measured in the 400- to 1,400-nm spectral range by using a spectrophotometer. The reflectance and transmittance data were analyzed by using an inverse adding-doubling algorithm to obtain the absorption (mu(a)) and reduced scattering (mu(a)') coefficients. A multichannel thermal probe controller system and infrared imaging radiometer methods were applied to measure the thermal properties of cartilage. The multichannel thermal probe controller system was used as an invasive technique to measure thermal conductivity and diffusivity of cartilage at three temperatures (27, 37, 50 degrees C). An infrared imaging radiometer was used as a noninvasive method to measure the thermal diffusivity of cartilage by using a CO(2) laser source (lambda = 10.6 microm) and an infrared focal plane array (IR-FPA) camera. RESULTS: The optical absorption peaks at 980 nm and 1,180 nm in cartilage were observed and corresponded to known absorption bands of water. The determined reduced scattering coefficient gradually decreased at longer wavelengths. The thermal conductivity values of cartilage measured by using an invasive probe at 27, 37, and 50 degrees C were 4.78, 5.18, and 5.76 mW/cm degrees C, respectively. The corresponding thermal diffusivity values were 1.28, 1.31, and 1.40x 10(-3) cm(2)/sec. Because no statistically significant difference in thermal diffusivity values with increasing temperature is found, the average thermal diffusivity is 1.32 x 10(-3) cm(2)/sec. The numerical estimate for thermal diffusivity obtained from infrared radiometry measurements was 1.38 x 10(-3) cm(2)/sec. CONCLUSION: Values of the spectral dependence of the optical absorption and reduced scattering coefficients, and thermal conductivity and diffusivity of cartilage were measured. The invasive and noninvasive diffusivity measurements were consistent and concluded that the infrared imaging radiometric technique has an advantage to determine thermal properties, because damage to the cartilage sample may be avoided. The measured values of absorption and reduced scattering coefficients can be used for predicting the optical fluence distribution in cartilage and determining optical source wavelengths for the laser-assisted cartilage reshaping studies. The thermal conductivity and diffusivity values can play role in understanding thermal-dependent phenomenon in cartilage during laser irradiation and determining laser dosimetry for the laser-assisted cartilage reshaping studies.

Animals↗
PubMed1990

Activation of benzo(a)pyrene-7,8-dihydrodiol in rat uterus: an in vitro study.

Peroxidatic metabolism of benzo(a)pyrene-7,8-dihydrodiol by calcium containing extracts of rat uteri was investigated. Covalently bound and soluble metabolites of benzo(a)pyrene-7,8-dihydrodiol were quantitated by radiometry and high performance liquid chromatography, respectively. 1. Uterine extracts incubated with benzo(a)pyrene-7,8-dihydrodiol activated this proximate mutagen to protein binding metabolite(s). 2. Hydrogen peroxide increased the protein binding and yielded a substantial amount of benzo(a)pyrene-trans-anti-tetrahydrotetrol, suggesting the peroxyl-type free-radical epoxidation process. 3. The results indicate that rat uterine peroxidase is able to catalyze free-radical activation of benzo(a)pyrene-7,8-dihydrodiol by epoxidation to its 9,10-dihydrodiolepoxide, a known ultimate mutagen and carcinogen.

Animals↗
PubMed2001

Theramal, mechanical, optical, and morphologic changes in bovine nucleus pulposus induced by Nd:YAG (lambda = 1.32 microm) laser irradiation.

UNLABELLED: BACKGROUND AND OBJECTIVE To examine the biophysical effects of photothermal heating on herniated intervertebral discs during laser decompression surgery. STUDY DESIGN/MATERIALS AND METHODS: Ex vivo bovine nucleus pulposus specimens were irradiated with a Nd: YAG laser (lambda = 1.32 microm, 100 seconds exposure time, 9-31 W/cm(2), 4.8 mm spot diameter), whereas changes in tissue thermal, mechanical, and optical properties were monitored by using, respectively, infrared radiometry, tissue tension measurements, and diffuse reflectance from a HeNe probe laser. Morphologic changes and mass reduction were monitored by recording shape changes on video and weighing specimens before and after laser exposure. RESULTS: At power densities below 20 W/cm(2), evaporation of water and specimen volume reduction (shrinking) were consistently observed on video during irradiation. In contrast, above 20 W/cm(2), vapor bubbles formed within the specimen matrix and subsequently ruptured (releasing heated vapors). When radiometric surface temperature approaches approximately 60 to 70 degrees C (denaturation threshold for tissue), tissue tension begins to increase, which is consistent with observations of specimen length reduction. The onset of this change in tissue tension is also reflected in characteristic alterations in diffuse reflectance. With cessation of laser irradiation, a sustained increase in tissue tension is observed, which is consistent with changes in specimen length and volume. Higher laser power results in a faster heating rate and subsequently an accelerated tension change. Specimen mass reduction increased with irradiance from 19 to 72% of the initial mass for 9--31 W/cm(2), respectively. Irradiated specimens did not return to their original shape after immersion in saline (48 hours) in contrast to air-dried specimens (24 hours), which returned to their original shape and size. CONCLUSION: These observations suggest that photothermal heating results in irreversible matrix alteration causing shape change and volume reduction (observed on video and evidenced by the increase in tissue tension) taking place at approximately 65 degrees C. Inasmuch as high laser power results in vapor bubble formation and specimen tearing, the heating process must be controlled. Diffuse reflectance measurements provide a noncontact, highly sensitive means to monitor dynamically changes in tension of nucleus purposus.

Animals↗
PubMed2005

Synergistic enhancement of selective nanophotothermolysis with gold nanoclusters: potential for cancer therapy.

BACKGROUND AND OBJECTIVE: We developed a new approach that enhances selective photothermolysis of tumor through laser activation of synergistic phenomena around nanoclusters, which are self-assembled into cancer cells. STUDY DESIGN/MATERIALS AND METHODS: In vitro verification of this approach was performed by laser pulse irradiation (420-570 nm and 1064 nm; 8-12 nanosecond; 0.1-10 J/cm2) of MDA-MB-231 breast cancer cells targeted with primary antibodies to which 40-nm gold nanoparticles were selectively attached by means of secondary antibodies. Photothermal (PT) radiometry, thermolens techniques, electron microscopy, atomic force microscopy, silver and gold enhancing kits, and viability test (Annexin V-propidium iodide) were employed to study nanoparticle spatial organization, the dynamics of microbubble formation, and cell damage. RESULTS: The assembly of gold nanoclusters on the cell membrane was accompanied by increased local absorption and red-shifting as compared to cells that did not have nanoclusters. These effects were amplified by a silver-enhancing kit and pre-irradiation of cells with low laser-pulse energy. Finally, a significant increase in laser-induced bubble formation and cancer cell killing was observed using near-IR lasers (1064 nm). A cancer cell antigens was used to provide target specificity for nanoclusters formation making the cancer cells sensitive to laser activation. CONCLUSION: The described approach uses relatively small and simple gold nanoparticles offering more effective delivery to target. In addition, the further self-assembling of these nanoparticles into nanoclusters on live cells provides significant enhancement of laser-induced cell damage. These nanoclusters (gold "nanobombs") can be activated in cancer cells only by confining near-IR laser pulse energy within the critical mass of the nanoparticles in the nanoclusters.

Adenocarcinoma↗
PubMedDate not supplied

Use of low-temperature scanning electron microscopy to compare and characterize three classes of snow cover.

This study, which uses low-temperature scanning electron microscopy (LTSEM), systematically sampled and characterized snow crystals that were collected from three unique classes of snow cover: prairie, taiga, and alpine. These classes, which were defined in previous field studies, result from exposure to unique climatic variables relating to wind, precipitation, and air temperature. Snow samples were taken at 10 cm depth intervals from the walls of freshly excavated snow pits. The depth of the snow pits for the prairie, taiga, and alpine covers were 28, 81, and 110 cm, respectively. Visual examination revealed that the prairie snow cover consisted of two distinct layers whereas the taiga and alpine covers had four distinct layers. Visual measurements were able to establish the range of crystal sizes that occurred in each layer, the temperature within the pit, and the snow density. The LTSEM observations revealed the detailed structures of the types of crystals that occurred in the snow covers, and documented the metamorphosis that transpired in the descending layers. Briefly, the top layers from two of the snow covers consisted of freshly fallen snow crystals that could be readily distinguished as plates and columns (prairie) or graupel (taiga). Alternatively, the top layer in the alpine cover consisted of older dendritic crystal fragments that had undergone early metamorphosis, that is, they had lost their sharp edges and had begun to show signs of joining or bonding with neighboring crystals. A unique layer, known as sun crust, was found in the prairie snow cover; however, successive samplings from all three snow covers showed similar stages of metamorphism that led to the formation of depth hoar crystals. These changes included the gradual development of large, three-dimensional crystals having clearly defined flat faces, sharp edges, internal depressions, and facets. The study, which indicates that LTSEM can be used to enhance visual data by systematically characterizing snow crystals that are collected at remote locations, is important for understanding the physics of snowpacks and the metamorphosis that leads to potential avalanche situations. In addition, the metamorphosis of snow crystals must be considered when microwave radiometry is used to estimate the snow water equivalent in the winter snowpack, because large snow crystals more effectively scatter passive microwave radiation than small crystals.

Journal Article↗
PubMed1995

2-Aminofluorene bioactivation by human term placental peroxidase.

Earlier investigations from our laboratory demonstrated that human term placental peroxidase (HTPP) is capable of metabolism of xenobiotics and endogenous compounds. In this study, purified HTPP was found to bioactivate 2-aminofluorene (2-AF) in the presence of H2O2. 2-AF oxidation was studied spectrophotometrically while radiometry was employed to assess the bioactivation. The rate of oxidation and covalent binding to protein and DNA was dependent upon the pH of the reaction medium and the concentration of 2-AF, the enzyme, and H2O2. To observe maximal enzyme velocity of oxidation, the presence of 16.5 microM H2O2, 100 microM 2-AF, 37 micrograms of the enzyme protein/ml, and pH 7.2 was required. Under optimal assay conditions, the range of specific activity between 130 and 165 nmol of 2-AF oxidized/min/mg HTPP was observed. Using similar assay conditions, the magnitude of covalent binding of [3H]-2-AF to protein (BSA) and calf thymus DNA was found to be about 508 pmol bound/min/mg HTPP/mg BSA and 84 pmol bound/min/mg HTPP/mg DNA, respectively. Potassium cyanide and sodium azide, the known inhibitors of different peroxidases, significantly blocked both the oxidation and covalent binding of 2-AF in a dose dependent manner. These results strongly suggest that peroxidase may be one of the important pathways responsible for the bioactivation of arylamines in human term placenta.

Azides↗
PubMed2002

Proteasome-dependent turnover of protein disulfide isomerase in oxidatively stressed cells.

Generalized increases in protein oxidation and protein degradation in response to mild oxidative stress have been widely reported, but only a few individual proteins have actually been shown to undergo selective, oxidation-induced proteolysis. Our goal was to find such proteins in Clone 9 liver cells exposed to hydrogen peroxide. Using metabolic radiolabeling of intracellular proteins with [35S]cysteine/methionine, and analysis by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), we found at least three labeled proteins ("A," "B," and "C") whose levels were decreased significantly more than the generalized protein loss after mild oxidative stress. "Protein C" was excised from 2-D PAGE and subjected to N-terminal amino acid microsequencing. "Protein C" was identified as Protein Disulfide Isomerase or PDI (E.C. 5.3.4.1), and this identity was reconfirmed by Western blotting with a C-terminal anti-PDI monoclonal antibody. A combination of quantitative radiometry and Western blotting in 2-D PAGE revealed that PDI was selectively degraded and then new PDI was synthesized, following H2O2 exposure. PDI degradation was blocked by inhibitors of the proteasome, and by cell treatment with proteasome C2 subunit antisense oligonucleotides, indicating that the proteasome was largely responsible for oxidation-induced PDI degradation.

Animals↗
PubMed1997

A novel mechanism of glutathione conjugate formation by lipoxygenase: a study with ethacrynic acid.

Ethacrynic acid (EA), a diuretic drug, is known to interact with glutathione transferases in the presence of reduced glutathione (GSH) to yield an EA-SG conjugate. Here we present evidence for a new mechanism for the formation of EA-SG conjugate by a soybean lipoxygenase (SLO)-mediated reaction involving oxidation of GSH to a GS.. Similar to the glutathione transferase-mediated reaction, EA-SG conjugate generated by SLO exhibited an absorbance maximum at 270 nm. The conjugate formation was dependent on the concentration of linoleic acid, EA, GSH, and SLO. The optimal assay conditions to observe a maximal rate of EA-SG formation required the presence of 0.4 mM linoleic acid, 1 mM GSH, 50 nM SLO, and 0.2 mM EA at pH 9.0. Classical inhibitors of lipoxygenase, e.g., nordihydroguaiaretic acid, gossypol, and 5,8,11-eicosatriynoic acid, significantly inhibited EA-SG conjugation. The SLO-generated EA-SG was isolated as a single peak by HPLC. Quantitation of EA-SG by HPLC-coupled radiometry using [3H]GSH yielded a rate of 16.5 mumol/min/mg SLO protein. This rate is up to 1650-fold greater than that reported for different purified isozymes of mammalian glutathione transferase. The structure of EA-SG isolated from HPLC column was confirmed by matrix-assisted laser desorption mass spectroscopy. These results suggest that lipoxygenase, which is primarily known for xenobiotic oxidation, may represent yet another important pathway for GSH conjugate formation that could lead to detoxification of certain chemicals.

Animals↗
PubMed1987

Heat delivery and thermometry in clinical hyperthermia.

This chapter has discussed some recent technical developments and trends in clinical hyperthermia. Several techniques for the treatment of tumours within 3-4 cm of the body surfaces were described. Each technique has its minor advantages and disadvantages; all techniques employing a single applicator produce temperature distributions with considerable gradients. The introduction of microwave and ultrasound techniques using multiple applicators in which there is some control of the pattern of the energy deposition within the treatment area should improve superficial treatments in this respect. A number of electromagnetic devices for regional hyperthermia are being developed and evaluated. The theoretical predictions of their performances are beginning to suggest restrictions to their use; the limited clinical experience is in general agreement with these predictions. Scanned and focussed ultrasound beams may offer the unique possibility of non-invasive, deep, yet localised hyperthermia in some locations. Such systems are at an early stage of their development; if they prove successful, their controlled and safe use will require detailed information of the temperature distributions produced. Invasive methods for inducing hyperthermia can produce relatively good temperature distributions. The development of 'constant temperature seeds' is promising. Both RF and microwave interstitial systems offering individual control of power to several channels should lead to improved temperature distributions. In general, non-invasive thermometry in clinical hyperthermia remains a distant goal, although developments in microwave radiometry may lead to systems with suitable spatial, temporal and temperature resolutions for use in superficial treatments. Invasive thermometry techniques can provide temperature measurements from several points or from along tracks within the treatment volume. The development of computer models to infer temperature distributions from the limited information available will be a major step in quantifying hyperthermal treatments.

Humans↗
PubMed1991

Comparison of arachidonate metabolism by alveolar macrophages from bighorn and domestic sheep.

We have defined the metabolites of arachidonic acid (AA) secreted by alveolar macrophages (AMs) of bighorn sheep and domestic sheep in response to three agents: calcium ionophore A23187, phorbol myristate acetate (PMA), and opsonized zymosan. Cells were labeled with [3H]AA prior to stimulation and 11 tritiated metabolites, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs), were detected and quantitated by high-performance liquid chromotography and radiometry. Zymosan stimulation resulted in the release of significantly elevated quantities (P less than 0.05), of LTB4, [5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid], 5-HETE, [5(S)-hydroxyeicosatetraenoic acid], and the nonenzymatic isomers of LTB4, [LTB I, 5(S),12(R)-6-trans-LTB4] and LTB II, [5(S), 12(S)-6-trans-LTB4], from domestic sheep AM when compared to bighorn sheep AM. Phorbol myristate acetate (PMA) stimulation released significantly elevated quantities (P less than 0.04), of TXB2, (thromboxane B2), HHT, [12(S)-12-hydroxy-5,8,10-heptadecaenoic acid], LTB I, LTB II, and 15-HETE, [15(S)-hydroxyeicosatetraenoic acid] from domestic sheep AMs when compared to bighorn sheep AMs. However, after A23187 challenge, only 15-HETE was significantly elevated (P less than 0.04) in domestic sheep AMs when compared to bighorn sheep AMs. These clear differences in AA metabolism of AMs obtained from bighorn and domestic sheep in response to three different agonists suggest not only different control mechanisms for lung metabolism of AA in the two species, but also suggest that differences in the metabolites released may lead to quite different regulation of lung defense mechanisms in the two sheep species.

Animals↗
PubMedDate not supplied

Autoradiographic and biochemical studies of drug distribution in the liver. III. [14C]Aminotriazole.

Whole body autoradiography revealed that the distribution pattern of [14C]aminotriazole in the mouse liver was homogeneous after intravenous administration of the labeled agent and then became heterogeneous (or reticular). Microautoradiography by dry-mounting method revealed that the macroscopic heterogeneous pattern was due to the central localization of the radioactive compound in the hepatic lobule. The present studies indicated that the heterogeneous distribution could be explained as follows. The amount of [14C]aminotriazole circulated to the liver was large since the compound was not so significantly distributed in non-hepatic tissues: distribution pattern was homogeneous in the liver. This was shown by whole body autoradiography and radiometry of tissues. A part of [14C]aminotriazole radioactivity present in the liver was gradually bound covalently to hepatic macromolecules. This was shown by whole body autoradiography after whole body sections of the mouse were extracted by acid, and by the biochemical fractionation of the liver. The covalently bound radioactivity alone became apparent in centrilobular hepatocytes: the distribution was heterogeneous. This was shown by microautoradiography and by the finding that the elimination rate of the bound radioactivity was slower than that of unbound radioactivity.

Amitrole↗
PubMed1998

Urothelial synthesis of prostanoids in the ovine ureter.

The purpose of this study was to investigate the site of production (urothelium/smooth muscle) and quantitative release of prostanoids in the ureter. Quantitative analysis of prostacyclin (PGI2) was by its metabolite, 6-keto PGFalpha, thromboxane (TXB2) and prostaglandin F2alpha. Synthesis by radiometry and radioimmunoassay was performed in vitro in sheep ureter specimens before and after removal of the inner epithelial layer and after addition of indomethacin. The major prostanoids present in the ureter were PGI2 and TXB2; PGI2 was quantitatively the largest component. Removal of the thin inner epithelial layer (urothelium) reduced mostly PGI2; addition of arachidonic acid significantly augmented PGI2 only in ureters with intact urothelium but did not alter TXB2 levels. The main source of prostanoid synthesis (PGI2) of the ureter is to be found in the urothelium. The functional role of the prostanoids may be related to coordination of peristalsis.

6-Ketoprostaglandin F1 alpha↗
PubMed1979

Radiometric assessment of experimental autoimmune encephalomyelitis in mice.

The cell-mediated inflammatory component of experimental autoimmune encephalomyelitis (EAE) in mice is measured by the radioisotopic technique. Mice are challenged with autologous spinal cord homogenate in Freund's complete adjuvant and at various time intervals after such immunization given [125I]5-iodo-2'-deoxyuridine which is incorporated into the mononuclear cell pool. The degree of cell-mediated inflammation is determined by radiometry of the brain and spinal cord tissues. Increased radiolabelling is detected in the brains 2 days prior to the onset of clinical signs of EAE; increased radioactivity of the spinal cord is concomitant with clinical signs. This technique is useful in staging the extent of EAE and may prove to be a powerful tool in studying cell-mediated reactions in other autoimmune diseases.

Animals↗
PubMed1995

Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia.

Animal studies and cell culture experiments demonstrated that posttranscriptional editing of the transcript of the GluR-2 gene, resulting in substitution of an arginine for glutamine in the second transmembrane region (TM II) of the expressed protein, is associated with a reduction in Ca2+ permeability of the receptor channel. Thus, disturbances in GluR-2 RNA editing with alteration of intracellular Ca2+ homeostasis could lead to neuronal dysfunction and even neuronal degeneration. The present study determined the proportions of edited and unedited GluR-2 RNA in the prefrontal cortex of brains from patients with Alzheimer's disease, in the striatum of brains from patients with Huntington's disease, and in the same areas of brains from age-matched schizophrenics and controls, by using reverse transcriptase-polymerase chain reaction, restriction endonuclease digestion, gel electrophoresis and scintillation radiometry. In the prefrontal cortex of controls, < 0.1% of all GluR-2 RNA molecules were unedited and > 99.9% were edited; in the prefrontal cortex both of schizophrenics and of Alzheimer's patients approximately 1.0% of all GluR-2 RNA molecules were unedited and 99% were edited. In the striatum of controls and of schizophrenics, approximately 0.5% of GluR-2 RNA molecules were unedited and 99.5% were edited; in the striatum of Huntington's patients nearly 5.0% of GluR-2 RNA was unedited. In the prefrontal white matter of controls, approximately 7.0% of GluR-2 RNA was unedited. In the normal human prefrontal cortex and striatum, the large majority of GluR-2 RNA molecules contains a CGG codon for arginine in the TMII coding region; this implies that the corresponding AMPA receptors have a low Ca2+ permeability, as previously demonstrated for the rat brain. The process of GluR-2 RNA editing is compromised in a region-specific manner in schizophrenia, in Alzheimer's disease and Huntington's Chorea although in each of these disorders there is still a large excess of edited GluR-2 RNA molecules. Disturbances of GluR-2 RNA editing leading to excessive Ca2+ permeability, may contribute to neuronal dysfunction in schizophrenia and to neuronal death in Alzheimer's disease and Huntington's disease.

Aged↗