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R M Kessler

Publications and source records attributed to R M Kessler.

At least 19 recordsLinked to original sources
PubMed1992

Visualization of extrastriatal dopamine D2 receptors in the human brain.

[123I]Epidepride, a potent and selective dopamine D2 radioligand, was administered to a 27 year old normal male volunteer. Single photon tomography revealed that peak striatal uptake occurred at 4 h after injection with a striatal:cerebellar ratio of 7.8 rising to over 100 at 18 h post injection. Uptake above the levels seen in cerebellum was also noted in the thalamus, pituitary, hypothalamus and temporal lobe, particularly medially. Single photon tomography with [123I]epidepride allows visualization of extrastriatal dopamine D2 receptors in man.

Adult↗
PubMed1992

Autoradiographic localization of dopamine D1 and D2 receptors in rat cerebral cortex following unilateral neurotoxic lesions.

Relative to dopaminergic innervation of cortex, dopamine D1 and D2 receptors may be located on presynaptic terminals and/or postsynaptically on cortical neurons. To assess the relative distribution of these sites, quantitative in vitro receptor autoradiography was performed following injection of 6-hydroxydopamine (6-OHDA) into the median forebrain bundle (MFB; which lesions presynaptic DA terminals) and ibotenic acid into the prefrontal and anterior cingulate cortices (which lesions neurons whose cell bodies are intrinsic to cortex). Receptor autoradiography was performed ten days after injection of neurotoxins with [3H]SCH 23390 (a D1 probe) and [125I]epidepride (a D2 probe). Both DA receptor subtypes were found in all layers of anterior cingulate and prefrontal cortices but were concentrated in deeper layers V and VI. Ibotenic acid lesion of cortex reduced D1 and D2 receptors by 55-80%, although the concentrations of DA and its major metabolite dihydroxyphenylacetic acid (DOPAC) were unchanged. Lesion of MFB produced no significant change in D1 and D2 receptors, but was associated with a 49-52% decrease in DA and DOPAC levels relative to the contralateral side. These results suggest that the majority of D1 and D2 receptors in prefrontal and anterior cingulate cortices are located postsynaptically on neurons intrinsic to the cortex.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Noninvasive detection of heart transplant rejection with positron emission scintigraphy.

Positron emission tomography has recently been used to evaluate ischemic heart disease through changes in myocardial blood flow and carbohydrate metabolism. Positron-emitting tracers were evaluated for their ability to detect acute allograft rejection after heterotopic cardiac transplantation in the rat. Sham-operated controls, nonrejecting isografts, and rejecting allografts were evaluated. Decay-corrected uptake of 13NH3 and 18F 2-fluoro 2-deoxyglucose (FDG) reflects blood flow and glucose flux, respectively. Histologic examination of rejecting allografts documented mild rejection at 4 days and severe acute rejection by 8 days. All isografts were free from rejection. Uptake of FDG is greater in rejecting allografts than in nonrejecting isografts during both severe rejection (2.4% +/- 0.8% versus 0.7% +/- 0.4%; p less than 0.02) and mild rejection (2.1% +/- 0.6% versus 0.4% +/- 0.1%; p less than 0.02). Uptake of NH3 in severely rejected grafts is reduced compared with nonrejecting grafts (0.6% +/- 0.3% versus 1.7% +/- 1.1%; p less than 0.02). There is no difference in NH3 uptake during mild rejection (1.8% +/- 0.7% versus 1.3% +/- 0.3%; p greater than 0.05). Uptake of FDG and NH3 in native hearts of animals from all experimental groups is not significantly different from that in sham-operated controls. Glucose may be a preferred metabolic substrate during rejection. Our data support a humoral mechanism for substrate preference during transplant rejection and a potential diagnostic role for positron emission tomography.

Ammonia↗
PubMed1992

Pulmonary artery sling with severe tracheobronchial stenosis: repair in infancy by tracheal resection and pulmonary artery reimplantation.

Pulmonary artery sling is an unusual anomaly. The results of surgical therapy have been unsatisfactory in the past because of poor long-term left pulmonary artery patency and failure to address concomitant primary tracheobronchial stenoses. Refinement of suture materials and microsurgical techniques have allowed earlier surgical treatment of tracheal stenosis and have led to improved pulmonary artery patency rates. Intermediate results of primary one-stage repair with tracheal resection and left pulmonary artery reimplantation or translocation in early childhood have been promising. It remains to be seen whether late anastomotic tracheal stenosis will be a problem. This constitutes the first report of a case of one-stage repair with tracheal resection and left pulmonary artery reimplantation in an infant.

Anastomosis, Surgical↗
PubMed1992

Positron emission tomography imaging-directed stereotactic neurosurgery.

The diagnostic yield of stereotactic biopsies depends upon safely sampling the most representative regions of masses. Potentially, localization information presently available from CT and MR scans might be improved by considering regional levels of cerebral metabolism by PET. In 10 selected stereotactic biopsies of intracranial mass lesions, PET scans were obtained using the Siemens CTI system; the Kelly-Goerss Compass system was used as the stereotactic development platform. PET-[18F]-fluorodeoxyglucose (FDG) images provided clinically significant information by appropriately directing biopsy efforts when CT and MRI was inconclusive or misleading. PET-FDG images can be successfully incorporated into routine image-directed stereotactic surgery.

Astrocytoma↗
PubMed1991

High affinity dopamine D2 receptor radioligands. 2. [125I]epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors.

Epidepride, (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2,3-dimethoxybenzamide+ ++, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist. Optimal in vitro binding required incubation at 25 degrees C for 4 h at pH 7.4 in a buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 1 mM MgCl2. Scatchard analysis of in vitro binding to striatal, medial frontal cortical, hippocampal and cerebellar membranes revealed a KD of 24 pM in all regions, with Bmax's of 36.7, 1.04, 0.85, and 0.37 pmol/g tissue, respectively. The Hill coefficients ranged from 0.91-1.00 in all four regions. The IC50's for inhibition of [125I]epidepride binding to striatal, medial frontal cortical, and hippocampal membranes for SCH 23390, SKF 83566, serotonin, ketanserin, mianserin, naloxone, QNB, prasozin, clonidine, alprenolol, and norepinephrine ranged from 1 microM to greater than 10 microM. Partial displacement of [125I]epidepride by nanomolar concentrations of clonidine was noted in the frontal cortex and hippocampus, but not in the striatum. Scatchard analysis of epidepride binding to alpha 2 noradrenergic receptors in the frontal cortex and hippocampus revealed an apparent KD of 9 nM. At an epidepride concentration equal to the KD for the D2 receptor, i.e. 25 pM, no striatal alpha 2 binding was seen and only 7% of the specific epidepride binding in the cortex or hippocampus was due to binding at the alpha 2 site. Correlation of inhibition of [3H]spiperone and [125I]epidepride binding to striatal membranes by a variety of D2 ligands revealed a correlation coefficient of 0.99, indicating that epidepride labels a D2 site. In vitro autoradiography revealed high densities of receptor binding in layers V and VI of prefrontal and cingulate cortices as well as in striatum. In vivo rat brain uptake revealed a hippocampal:cerebellar and frontal cortical:cerebellar ratio of 2.2:1 which fell to 1.1:1 following haloperidol pretreatment. These properties suggest that [125I]epidepride is a superior radioligand for the in vitro and in vivo study of striatal and extrastriatal dopamine D2 receptors.

Animals↗
PubMed1991

High affinity dopamine D2 receptor radioligands. 1. Regional rat brain distribution of iodinated benzamides.

Five 125I-labeled substituted benzamides, which are close structural analogues of (S)-sulpiride, eticlopride, and isoremoxipride, were evaluated for their selective in vivo uptake into dopamine D2 receptor rich tissue of the rat brain. "Iodopride" (KD 0.88 nM), an iodine substituted benzamide structurally related to sulpiride, displayed a maximal striatum: cerebellar uptake ratio of 7.6. Demonstration of saturation of the receptor with [125I]iodopride in striatum required uptake in frontal cortex to be used, rather than cerebellar uptake, to define nonspecific binding. Two other ligands structurally related to eticlopride, "iclopride" (KD 0.23 nM) and "itopride" (KD 0.16 nM), displayed maximal striatal: cerebellar uptake ratios of 9.8 and 3.3, respectively. The most potent ligands, "epidepride" (KD 0.057 nM) and "ioxipride" (KD 0.070 nM) showed striatal:cerebellar uptake ratios of 234 and 65, respectively. The observed uptake ratios correlated poorly with the affinity constants for the dopamine D2 receptor alone, but were highly correlated (r = 0.92) with the product of the receptor dissociation constant (KD) and the apparent lipophilicity (kw), as determined by reverse-phase HPLC at pH 7.5. Total striatal uptake also appeared dependent on lipophilicity, with maximal uptake occurring for ligands having log kw 2.4-2.8.

Animals↗
PubMed1990

Cooperative T1 and T2 effects on contrast using a new driven inversion spin-echo (DISE) MRI pulse sequence.

A pulse sequence is presented for obtaining a single image with combined T1/T2 weighting. T2 relaxation is made to increase intensity, in cooperation with the effect of T1 relaxation, by providing T2 weighting with a 90 degrees-180 degrees-90 degrees driven inversion pulse triplet in an inversion recovery method. Unlike the inversion spin-echo method having a short inversion time (TI), signals in the new driven inversion spin-echo (DISE) method need not be negative and the most T1-sensitive region of the recovery curve can be used. Selecting sensitivity to one relaxation time does not degrade the sensitivity to the other relaxation time. T1 sensitivity is thus extended to longer echo times (TE intervals). T2 sensitivity is extended to longer TI intervals, and the combined T1/T2-weighted technique with intermediate TE and TI has highly cooperative and near-maximal T1 and T2 effects on contrast. Intensity is not multiplicatively degraded by T1 and T2 weighting so that the signal-to-noise of the combined T1/T2-weighted method is high. High intensity and T1 and T2 cooperatively occur for a much wider range of relaxation times, and especially for images heavily weighted to the pathologic intermediate and long T1 and T2 regime.

Brain↗
PubMed1990

Gadolinium-enhanced MR angiography.

Experience in three patients (one each with meningioma, pineal tumor, and prominent jugular bulb) illustrates that magnetic resonance (MR) angiography can benefit from the administration of gadolinium diethylenetriaminepentaacetic acid. Data were acquired with a three-dimensional velocity-compensated (fast imaging with steady-state precession) sequence. MR angiograms were obtained with a ray projection algorithm by using maximum intensity values. Portions of the vascular anatomy--particularly venous structures and smaller arteries--were better portrayed on the postcontrast than on the precontrast angiograms. Enhancing lesions were also seen on the projection images. Enhancement of dura and extracranial tissues (sinus and nasal mucosa) can obscure vascular detail.

Adult↗
PubMed1990

Sodium-dependent isomerization of dopamine D-2 receptors characterized using [125I]epidepride, a high-affinity substituted benzamide ligand.

We have characterized the in vitro binding of a new ligand, [125I]epidepride, and used this substituted benzamide to assess the sensitivity of dopamine D-2 receptors to sodium. Both direct and indirect binding studies with [125I]epidepride and unlabeled epidepride, respectively, demonstrated that the affinity of D-2 receptors for the ligand was decreased from 20 to 30 pM in the presence of sodium to 350 to 500 pM in the absence of sodium. The density of binding sites for [125I]epidepride was identical in the presence and absence of NaCl. The time courses for association of [125I]epidepride to and dissociation from D-2 receptors in the presence of sodium were not consistent with simple bimolecular reactions, suggesting the possibility of a sodium-dependent ligand-induced receptor isomerization. Thus, dissociation of [125I]epidepride was biphasic in the presence of sodium, but monophasic in the absence of sodium. The rank order of potency for inhibition of [125I]epidepride binding by drugs was identical in rat striatum and cells expressing a D-2 receptor cDNA, and similar to the previously described pharmacological profile of D-2 receptors labeled by [3H]spiperone. [125I]Epidepride bound to two classes of binding sites in rat medial prefrontal cortex. One class, present at a density of 10 fmol/mg of protein and with a Kd value of approximately 40 pM, was pharmacologically indistinguishable from D-2 receptors in striatum and transfected cells. The pharmacological profile of the second class of sites was similar to that of alpha-2 adrenergic receptors. [125I]Epidepride had 50- to 100-fold lower affinity (approximately 2 nM) for alpha-2 receptors than for D-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

(S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-[125I]iodo- 2-methoxybenzamide hydrochloride, a new selective radioligand for dopamine D-2 receptors.

From salicyclic acid, the two enantiomers of N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-iodo-2-methoxybenzamide (6b) were prepared in a five-step synthesis. With use of Heindel's triazene method for introduction of the radionuclide, the iodine-125-labeled substituted benzamide was obtained with a calculated specific activity of 136 Ci/mmol and 14% radiochemical yield. For the preparation of the iodine-125-labeled benzamide with higher specific activity, this method was unsuccessful and utilization of the corresponding tri-n-butyltin derivative was required. Treatment of the latter in dilute hydrochloric acid with sodium iodide-125 and chloramine-T gave [125I](S)-6b in 56% radiochemical yield and at least 97% radiochemical purity. The displacement of [125I](S)-6b and [3H](S)-sulpiride from their respective binding sites in striatal rat brain homogenates using various neuroleptic agents showed that (S)-6b has the same binding profile but more potent binding for dopamine D-2 receptors than has sulpiride. These experiments also indicate that the S enantiomer of 6b is a specific ligand (KD = 1.2 nM) for the D-2 receptor. Further, the octanol-water partition coefficient of (S)-6b as determined by reverse-phase high-performance liquid chromatography was found to be 40 times greater than that for sulpiride. Thus (S)-6b has a lipophilicity that will allow a relatively higher uptake into the brain compared to sulpiride. In vivo experiments with rats show that [125I](S)-6b penetrates readily into the brain and is preferentially localized in the striatum as compared to the cerebellum, the ratio of uptake being 7.2 to 1, 60 min after injection. These observations of good brain penetration and high affinity and selectivity for D-2 receptors indicate that the corresponding iodine-123-labeled benzamide may be a useful ligand for the noninvasive visualization study of dopamine D-2 receptor sites in vivo by single photon emission computed tomography.

Animals↗
PubMed1988

Central nervous system lesions in pediatric patients: Gd-DTPA-enhanced MR imaging.

Twenty pediatric patients, aged 2-18 years, with known or suspected masses in the brain and/or spinal cord were studied with magnetic resonance imaging at 0.6T with and without use of 0.1 mmol/kg gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The multisection, multiecho imaging mode was utilized. Surgically proved mass lesions included astrocytoma (n = 6), medulloblastoma (n = 2), ependymoma (n = 1), craniopharyngioma (n = 1), oligodendroglioma (n = 1), germinoma (n = 1) and fibrosarcoma (n = 1). Presumptive diagnoses included astrocytoma (n = 3), arachnoid cyst (n = 1), tuberous sclerosis (n = 1), cryptic vascular malformation (n = 1), and normal (n = 1). There was dramatic enhancement in 11 of 20 patients, with improved definition of the presence and extent of lesions in six patients. No adverse effects were noted in any of the 20 patients. It is concluded that Gd-DTPA is useful in delineating the presence, extent, and number of certain lesions of the central nervous system in children.

Adolescent↗
PubMed1987

MRI of mumps encephalitis: comparison with CT evaluation.

The evaluation of a patient with mumps encephalitis by computed tomography (CT) and magnetic resonance (MR) imaging is reported. Correlation of findings on MR and CT in relation to clinical symptoms is presented. MR was found to be more sensitive in the number of lesions detected (11) as compared to CT (3). Thus, it seems that MR imaging may be a sensitive diagnostic adjunct in cases of suspected viral encephalitis.

Child, Preschool↗
PubMed1987

Magnetic resonance brain tumor imaging in canine glioma.

This study investigates a canine model of experimental brain tumor. Particularly addressed was the usefulness of gadolinium contrast-enhanced MRI for differentiating brain tumor tissue from cerebral edema. Cultured canine glioma cells were injected into the left hemispheres of six adult mongrel dogs. All dogs developed brain tumors. Serum samples drawn prior to and serially after tumor inoculation showed development of antibodies reactive to the tumor. All tumors were visualized with MRI. Contrast-enhanced T1-weighted imaging was the most sensitive with gadolinium producing tumor enhancement due to blood-brain barrier breakdown. Gross and microscopic autopsy findings correlated well with MRIs.

Animals↗
PubMed1985

Clinical history, brain metabolism, and neuropsychological function in Alzheimer's disease.

Data concerning 7 patients with a diagnosis of presumptive Alzheimer's disease (mean age, 65.6 years) are presented in detail in relation to the patients' regional cerebral metabolic rates for glucose. Rates were measured by positron emission tomography with fluorine 18-labeled fluoro-2-deoxy-D-glucose under conditions of reduced visual and auditory stimulation. A relationship was found between severity of dementia and brain metabolism. In patients with mild to moderate Alzheimer's disease, memory and intellectual deficits were evident without major reductions in absolute metabolic rates, while ratios of regional to whole brain metabolism revealed reductions in regions of the parietal lobes. In the late, severe form of the disease, brain metabolic rates were consistently and significantly reduced. The findings suggest that memory and intellectual deficits are reflected in reductions of brain metabolism in some brain regions in mild to moderate forms of Alzheimer's disease and that, in the late, severe form of the disease, reductions occur consistently throughout the brain.

Aged↗