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H Herzog

Publications and source records attributed to H Herzog.

At least 19 recordsLinked to original sources
PubMed1992

Cloned human neuropeptide Y receptor couples to two different second messenger systems.

Neuropeptide Y (NPY) is one of the most abundant neuropeptides in the mammalian nervous system and exhibits a diverse range of important physiological activities, including effects on psychomotor activity, food intake, regulation of central endocrine secretion, and potent vasoactive effects on the cardiovascular system. Two major subtypes of NPY receptor (Y1 and Y2) have been defined by pharmacological criteria. We report here the molecular cloning of a cDNA sequence encoding a human NPY receptor and the corrected sequence for a rat homologue. Analysis of this sequence confirms that the receptor is a member of the G protein-coupled receptor superfamily. When expressed in Chinese hamster ovary (CHO) or human embryonic kidney (293) cells, the receptor exhibits the characteristic ligand specificity of a Y1 type of NPY receptor. In the 293 cell line, the receptor is coupled to a pertussis toxin-sensitive G protein that mediates the inhibition of cyclic AMP accumulation. In the CHO cell line, the receptor is coupled not to the inhibition of adenylate cyclase but rather to the elevation of intracellular calcium. These results demonstrate that second messenger coupling of the NPY-Y1 receptor is cell type specific, depending on the specific repertoire of G proteins and effector systems present in any cell type.

Adenylyl Cyclases↗
PubMed1992

On the influence of spatial resolution and of the size and form of regions of interest on the measurement of regional cerebral metabolic rates by positron emission tomography.

Factors that affect the accuracy of the positron emission tomographic (PET) quantification of cerebral metabolic rates include the spatial resolution of the employed imaging device and the method used for extraction of regional metabolic values from the PET data set. The present article reviews (i) how and to what extent these two factors are presumed to influence the measurement of absolute values of cerebral metabolic rates and their ratios, and (ii) whether and how these factors may affect comparisons of regional metabolic rates between groups of subjects.

Brain↗
PubMed1992

Regional cerebral glucose consumption measured by positron emission tomography in patients with Wilson's disease.

Using positron emission tomography (PET), the regional cerebral metabolic rate of glucose consumption (rCMRGlc) was measured in 14 patients with Wilson's disease (WD) and 23 normal subjects. In WD patients, cerebellar, striatal and--to a lesser extent--cortical and thalamic rCMRGlc were significantly decreased compared with controls. Striatal rCMRGlc was significantly reduced in those 4 patients who had recently started decoppering therapy as compared with striatal rCMRGlc measured in those 10 patients with longer duration of medication. Caudate rCMRGlc correlated significantly with various signs of extrapyramidal dysfunction. Cerebellar, thalamic and cortical rCMRGlc correlated significantly with the severity of pyramidal signs. These data indicate that the PET measurement of rCMRGlc may be a useful tool to evaluate cerebral involvement in WD and to monitor the response to treatment.

Adult↗
PubMed1992

Individual somatotopy of primary sensorimotor cortex revealed by intermodal matching of MEG, PET, and MRI.

A method for comparing estimated magnetoencephalographic (MEG) dipole localizations with regional cerebral blood flow (rCBF) activation areas is presented. This approach utilizes individual intermodal matching of MEG data, of rCBF measurements with [15O]-butanol and positron emission tomography (PET), and of anatomical information obtained from magnetic resonance (MR) images. The MEG data and the rCBF measurements were recorded in a healthy subject during right-sided simple voluntary movements of the foot, thumb, index finger, and mouth. High resolution 3D-FLASH MR images of the brain consisting of 128 contiguous sagittal slices of 1.17-mm thickness were used. MEG/MR integration was performed by superimposing the 3D head coordinate system constructed during the MEG measurement onto the MR image data using identical anatomical landmarks as references. PET/MR integration was achieved by a phantom-validated iterative front-to-back-projection algorithm resulting in one integrated MEG/PET/MR image. The estimated dipole locations followed the somatotopic organisation of the task-specific rCBF increases as evident from PET, although they did not match point-to-point. Our results demonstrate that intermodal matching of MEG, PET and MR data provides a tool for relating estimated neuromagnetic field locations to task-specific rCBF changes in individual subjects. Our method offers the perspective of refined dipole modelling.

Adult↗
PubMed1992

A history of significant steroid discoveries and developments originating at the Schering Corporation (USA) since 1948.

A firsthand historical account of some of the significant contributions of the steroid research group at the Schering Corporation (Bloomfield, NJ, USA) to the discovery and/or development of important therapeutic agents is presented. These include the discovery of the antiinflammatory corticosteroid drugs prednisone, prednisolone, and betamethasone, all of which, more than 30 years after their introduction, continue to enjoy wide use in human and animal medical practice throughout the world.

Adrenal Cortex Hormones↗
PubMed1992

Individual integration of positron emission tomography and high-resolution magnetic resonance imaging.

We have developed, validated, and employed a technique of retrospective spatial alignment and integrated display of positron emission tomographic (PET) and high-resolution magnetic resonance (MR) brain images. The method was designed to improve the anatomical evaluation of functional images obtained from single subjects. In the first computational step, alignment of PET and MR data sets is achieved by iteratively matching in three orthogonal views the outermost scalp contours derived from front-to-back projections of each data set. This procedure avoids true three-dimensional modeling, runs without user interaction, and tolerates missing parts of the head circumference in the image volume, as usually the case with PET. Thereafter, high-resolution MR sections corresponding to the PET slices are reconstructed from the spatially transformed MR data. In a phantom study of this method, PET/MR alignment of the phantom's surface was accurate with average residual misfits of 2.17 to 2.32 mm as determined in three orthogonal planes. In-plane alignment of the phantom's insertion holes was accurate with an average residual misfit of 2.30 mm. In vivo application in six subjects allowed the individual anatomical localization of regional CBF (rCBF) responses obtained during unilateral manual exploration. In each subject, the maxima of the rCBF activations in the hand area were precisely allocated to gray matter in the anterior or posterior wall of the central sulcus. The configuration of the rCBF responses closely followed the gyral structures. The technique provided a better topographical understanding of rCBF changes in subtraction images of PET activation studies. It opens the perspective for studies of structural-functional relationships in individual subjects.

Brain↗
PubMed1992

Frontal lobe function in amyotrophic lateral sclerosis: a neuropsychologic and positron emission tomography study.

In this study the regional cerebral glucose utilization and the neuropsychological performance of patients with amyotrophic lateral sclerosis (ALS) was investigated. Special attention was given to neuropsychological tests thought to mirror frontal lobe dysfunction. The regional cerebral glucose utilization was studied in 18 patients using high-resolution positron emission tomography. Clinically all patients displayed upper and lower motor neurone signs. In ALS patients glucose metabolism was significantly reduced in the frontal and in the entire cortex compared with controls; no changes were seen in the cerebellum. Comprehensive neuropsychological assessment of ALS patients compared to a pair matched control group revealed mild frontal dysfunction which in part significantly correlated with reduced glucose metabolism in the cortex and subcortical structures. We conclude that in patients with ALS, glucose consumption is decreased in parts of the brain other than the motor cortex accompanied by mild neuropsychological deficits based on the tests employed in this study.

Adult↗
PubMed1992

Fluorescence in situ mapping of the human nuclear NAD+ ADP-ribosyltransferase gene (ADPRT) and two secondary sites to human chromosomal bands 1q42, 13q34, and 14q24.

A 3.5-kb cDNA probe containing the 23 exons from the coding sequence of human nuclear NAD+ ADP-ribosyltransferase (poly [ADP-ribose] polymerase [ADPRT], E.C.2.4.2.30) was used to map the gene and two additional sites by nonisotopic in situ chromosomal hybridization. The previous localization of the structural gene on 1q42 was confirmed. Two other hybridization peaks on 13q34 and 14q24 suggested the presence of ADPRT pseudogenes.

Chromosome Mapping↗
PubMed1992

Noninvasive assessment of regional cardiac adenosine using positron emission tomography.

One of the early metabolic changes associated with myocardial ischemia is the breakdown of adenine nucleotides resulting in the enhanced production of adenosine. In order to image regional cardiac adenosine by positron emission tomography (PET) the enzymatic conversion of adenosine into [11C]-S-adenosylhomocysteine ([11C]SAH) was used in the presence of 11C-labeled homocysteine thiolactone (adenosine + [11C] - homocysteine-->[11C] - SAH + H2O). Following production of an experimental coronary constriction in anesthetized dogs carrier added 1-[11C]-D,L-homocysteine thiolactone (5-27 mCi, 30 mg/kg) was infused over 1 min. This intervention, while hemodynamically ineffective, increased the plasma homocysteine concentration from 2.5 to 306 microM, which thereafter declined with a T1/2 of 28 min to 97 microM after 60 min. During the first minutes following infusion of [11C] homocysteine, the radioactivity concentration in the blood pool, the nonischemic and the ischemic myocardium were similar. Between 20 and 60 min, however, the regional radioactivity concentration was highest in the perfusion area of the stenosed vessel: 6.6% compared to 5.2 and 5.2% of the injected dose per 1 I tissue. The elevated radioactivity concentration was strictly confined to the perfusion area of the occluded artery. Using [35S]-L-homocysteine (20 microCi; 30 mg/kg) chromatographic separation of SAH in tissue extracts confirmed that the radioactivity accumulation was due to trapping of adenosine in the cellular SAH-pool. These experiments provide first evidence that 1-[11C]homocysteine thiolactone can be successfully used to assess regional adenosine formation in the heart with PET via measurement of [11C] SAH accumulation.

Adenosine↗
PubMed1991

Effect of Huntington's and Alzheimer's diseases on the transport of nicotinic acid or nicotinamide across the human blood-brain barrier.

The cerebral uptake of 11C-nicotinic acid (11C-NAC) and 11C-nicotinamide (11C-NAM) was quantified by the use of PET. Based on the amount of activity injected, the PET images showed a low cerebral uptake of 11C-NAC, while 11C-NAM was clearly visualized in the cortical areas. This discrepancy was found to be the result of the binding of 11C-NAC to the red blood cells by a factor of 5 to 20 above that for 11C-NAM. 11C-NAM was better extracted by the cerebrum than 11C-NAC, as shown by the mean values of the cortical tissue/plasma ratio of 1.9 for 11C-NAC and 5 for 11C-NAM at 30 min. post-injection. An analysis of Patlak-Gjedde plot curves revealed a metabolic compartment for 11C-NAC and 11C-NAM with similar values of about 0.02 l/min for the accumulation constant K3. This was indicative of a slower transport rate for 11C-NAC. A significant finding of the study was the increasing ratio of activity concentrations in red blood cells versus the concentrations in plasma (over time). There were no significant differences between the data from normal volunteers and patients with Huntington's or Alzheimer's disease.

Alzheimer Disease↗
PubMed1991

Effects of varying physical parameters of a PET system on the accuracy of radioactivity quantitation in vivo.

The accuracy of quantitation of radioactivity by positron emission tomography (PET) is dependent on design parameters which differ among the PET-cameras in use today. Using a high resolution PET camera (Scanditronix PC 4096-15WB) we have simulated various of these parametric design differences such as xy- and z-resolution, slice thickness, methods of scatter and attenuation correction. The quantitation of actual patient data differed by up to 40% for both static and dynamic data when single parameters were varied to fit cameras of preexisting and recent design. For example, we found that cortical FDG data are 15% lower for 11 mm image resolution than for 5.5 mm image resolution, and striatal uptake of a D2-receptor-ligand decreases by 25% when the slice thickness is 14 mm instead of 7 mm. In general, the errors due to the single effects studied here are expected to be cumulative, leading to an even greater discrepancy in the overall performance of older PET cameras when compared to those of recent design.

Brain↗
PubMed1991

Brain and brain tumor uptake of L-3-[123I]iodo-alpha-methyl tyrosine: competition with natural L-amino acids.

SPECT studies with L-3-[123I]iodo-alpha-methyl tyrosine (IMT) were carried out in 10 patients with different types of brain tumors--first under fasting conditions (basal) and a week later during intravenous infusion of a mixture of naturally-occurring L-amino acids (AA load). An uptake index (UI) was calculated by dividing tissue count rates by the integral of plasma count rates. The UI decreased by 45.6% +/- 15.4% (n = 10, p less than 0.001) for normal brain and by 53.2% +/- 14.1% for gliomas (n = 5, p less than 0.01) during AA load compared to basal conditions, while two meningiomas and a metastasis showed only a minor decrease (23.9 +/- 5.7%, n.s.). Two pituitary adenomas could not be delineated on the SPECT scans. These data indicate that IMT competes with naturally-occurring L-amino acids for transport into normal brain and gliomas. Transport characteristics of IMT into tumors of nonglial origin appear to be different from those of gliomas. For both types of tumors, it is advisable to perform IMT-SPECT under fasting conditions.

Adult↗
PubMed1991

The comparison of 2-18F-2-deoxyglucose and 15-(ortho-123I-phenyl)-pentadecanoic acid uptake in persisting defects on thallium-201 tomography in myocardial infarction.

The myocardial uptake of glucose and fatty acids into 201Tl redistribution defects were studied in 32 patients with myocardial infarction by tomography using 2-18F-2-deoxyglucose (FDG) and 15-(ortho-123I-phenyl)-pentadecanoic acid (oPPA). A total of 1153 segments were analyzed, 408 (35%) of which showed a persistent thallium-defect in stress-redistribution images. Of the segments with a decreased 201Tl uptake in these redistribution tomograms, 50.5% had a decreased uptake of both FDG and oPPA; in 21.8% FDG as well as oPPA uptake was within normal range. Normal FDG uptake but decreased oPPA uptake was detected in 17.4%, whereas 10.3% of the segments had normal oPPA uptake but decreased FDG uptake (chi-square test, p less than 0.001). A significant correlation of FDG and oPPA uptake (r = 0.51) was found in the segments with persistent 201Tl defect. Thus, a substantial fraction of persistent thallium-defects after healed myocardial infarction exhibit FDG as well as oPPA uptake, probably due to residual fatty acid metabolism in partially ischemic regions.

Adult↗
PubMed1990

Normal striatal glucose consumption in two patients with benign hereditary chorea as measured by positron emission tomography.

Positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) was used to investigate the regional cerebral metabolic rate of glucose consumption (rCMRGlc) in two patients with benign hereditary chorea (BHC) and 21 normal subjects. Relative and absolute values of cerebellar, striatal, thalamic, and cortical rCMRGlc were within normal limits for both patients with BHC, indicating that the choreic movement disorder encountered in these two patients was not caused by a decrease of energy metabolism in the striatum such as that found regularly in most patients with other forms of chorea (e.g. Huntington's and Wilson's disease).

Adult↗
PubMed1990

Quantification of the whole-body distribution of PET radiopharmaceuticals, applied to 3-N-([18F]fluoroethyl)spiperone.

Using a multi slice whole body PET scanner PC4096-15WB, diagnostic measurements of the cerebral distribution of the D2 receptor ligand 3-N-([18F]fluoroethyl)spiperone were extended to quantify the biodistribution of this PET radiopharmaceutical. As a rotating line source was used for measured attenuation correction, transmission scans could be combined with emission scans even after injection of the tracer. Only 1% of the total administered dose (TAD) was found in the whole brain at 180 min, but the striatum and pituitary were still excellently delineated. Urinary bladder, gall bladder, and liver were the organs with the highest TAD ranging from 6% to 25%. The gall bladder is the critical organ with an absorbed dose of about 200 muGy/MBq followed by the urinary bladder and liver with 83 and 66 muGy/MBq, respectively. In the rest of the body radioactivity was evenly distributed. The total body dose was found to be 11.9 muGy/MBq.

Brain↗
PubMed1990

[Assessment of central disorders of the statoacusticus nerve using high resolution imaging procedures (PET and MRI)].

Disorders of the auditory and vestibular central nervous system can be diagnosed more precisely by high resolution magnetic resonance imaging (MRI) and positron emission tomography (PET). MRI is mostly used for small intrameatal acoustic neuromas up to 10 mm, intracranial cholesteatomas, and multiple sclerosis. Positron emission tomography has advantages after acoustic or electric stimulation in the auditory cortex. PET is not yet a routine procedure in clinical diagnosis.

Blood Glucose↗
PubMed1990

Compensatory mechanisms in patients with asymptomatic carotid artery occlusion.

Twelve patients with asymptomatic occlusion of one (n = 8) or both (n = 4) internal carotid arteries were examined by positron emission tomography (PET) and transcranial Doppler ultrasound. PET measurements included the determination of the regional cerebral blood flow (rCBF), oxygen extraction ratio (rOER), cerebral metabolic rate of oxygen (rCMRO2), and cerebral metabolic rate of glucose consumption (rCMRGlc). Transcranial Doppler ultrasound (TCD) was used to determine the pathways and efficacy of collateralization via the circle of Willis and included spectrum analysis of flow velocities within the middle and anterior cerebral arteries as well as vasoreactivity tests. In correspondence with ultrasound evidence of a haemodynamically effective intracranial collateral circulation no significant differences between patients and controls were observed for rOER, rCMRO2 and rCMRGlc, but rCBF was globally reduced. Furthermore, in all patients with unilateral carotid occlusion PET excluded side asymmetries of any parameter studied. In contrast, flow velocity parameters measured by TCD were significantly reduced ipsilateral and significantly increased contralateral to the carotid obstruction. Vasodilative capacities, however, remained preserved even in the territory of the occluded carotid system. These data indicate that patients with asymptomatic carotid occlusion compensate by haemodynamic and not by metabolic mechanisms in contrast to symptomatic patients.

Aged↗