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T Hagen

Publications and source records attributed to T Hagen.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Diffusion-weighted magnetic resonance tomography in diagnosis of encephalitis disseminata].

Magnetic resonance (MR) imaging is one of the best methods in diagnosis of multiple sclerosis, particularly in disclosure of active demyelinating lesions. Aim of this study was to compare diffusion weighted imaging and contrast enhancement in the detection of active lesions. A MR study with a contrast enhanced T1-weighted pulse sequence with magnetization transfer presaturation and a diffusion weighted echoplanar pulse sequence (b = 1000 s/mm2) was performed in 17 patients (11 women, 6 men) with multiple sclerosis. 29 of 239 lesions showed an increased signal intensity in diffusion weighted imaging, 24 lesions a contrast enhancement, but only 16 lesions were visible in both pulse sequences. In patients with short clinical symptomatology significant more lesions could be detected with diffusion-weighted pulse sequence in comparison to patients with long standing symptomatology showing more lesions with contrast enhancement. Hence it is likely, that both pulse sequences detect different histopathologic changes. The early detection of demyelinating lesions in diffusion weighted imaging is attributed to the extracellular edema, however the contrast enhancement is caused by a blood brain barrier abnormality. It can be expected that diffusion weighted imaging will have a high impact on imaging of multiple sclerosis not only in therapeutic trials, but also in clinical routine.

Adolescent↗
PubMed2000

[Surgical transvenous embolization of spontaneous carotid cavernous sinus fistulas in two patients].

BACKGROUND: Arteriovenous communications in which blood flows from meningeal branches of the internal and external carotid arteries into the venous circulation around and in the cavernous sinus are termed spontaneous (dural) carotid sinus cavernous fistulas. Due to their mostly low shunt volume they are rarely life threatening, but without treatment they may cause severe ocular complications like episcleral secondary glaucoma, central vein occlusion or exudative retinal detachment. Traditional therapy is the transarterial approach by an interventional neuroradiologist. If such an approach is not possible or unsuccessful a transvenous route has to be considered. PATIENTS AND METHODS: Two patients underwent anterior orbitotomy via sub brow incision or infraciliary incision with cannulation of the superior ophthalmic vein or the inferior ophthalmic vein and embolization of the cavernous sinus with platinum coils. RESULTS: Successful closure was achieved on angiography and normalisation of clinical symptoms after a short period of progressive venous congestion. CONCLUSIONS: For arteriovenous fistulas that cannot be embolized arterially the surgical transvenous orbital route may work as a method of second choice. When performed by an interdisciplinary team (orbital surgeon, interventionell neuroradiologist) it is a technically straightforward, effective and promising approach.

Aged↗
PubMed2000

Catalytic efficiency determines the in-vivo efficacy of PON1 for detoxifying organophosphorus compounds.

Human paraoxonase (PON1) is a polymorphic, high-density lipoprotein (HDL)-associated esterase that hydrolyzes the toxic metabolites of several organophosphorus (OP) insecticides and nerve agents. The activity polymorphism is determined by a Gln/Arg (Q/R) substitution at position 192. Injection of purified PON1 protects animals from OP poisoning. In the present study, we investigated the in-vivo function of PON1 for detoxifying organophosphorus insecticides in PON1-knockout mice that were challenged via dermal exposure with diazoxon, diazinon and paraoxon. PON1-knockout mice were extremely sensitive to diazoxon. Doses (2 and 4 mg/kg) that caused no cholinesterase (ChE) inhibition in wild-type mice were lethal to the knockout mice, which also showed slightly increased sensitivity to the parent compound diazinon. Surprisingly, these knockout mice did not show increased sensitivity to paraoxon. In-vitro assays indicated that the PON1R192 isoform hydrolyzed diazoxon less rapidly than did the PON1Q192 isoform. In-vivo analysis, where PON1-knockout mice received the same amount of either PON1(192) isoform via intraperitoneal (i.p.) injection 4 h prior to exposure, showed that both isoforms provided a similar degree of protection against diazoxon, while PON1R192 conferred better protection against chlorpyrifos-oxon than PON1Q192. Injection of purified rabbit PON1 or either human PON1(192) isoform did not protect PONI-knockout mice from paraoxon toxicity, nor did over-expression of the human PON1R192 transgene in wild-type mice. Kinetic analysis of the two human PON1(192) isoforms revealed that the catalytic efficiency (Vmax/Km) determines the in-vivo efficacy of PON1 for organophosphorus detoxication. The results indicate that PON1 plays a major role in the detoxication of diazoxon and chlorpyrifos oxon but not paraoxon.

Animals↗
PubMed2000

Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants.

The responses to oxidative stress induced by chronic exercise (8-wk treadmill running) or acute exercise (treadmill running to exhaustion) were investigated in the brain, liver, heart, kidney, and muscles of rats. Various biomarkers of oxidative stress were measured, namely, lipid peroxidation [malondialdehyde (MDA)], protein oxidation (protein carbonyl levels and glutamine synthetase activity), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), and endogenous antioxidants (ascorbic acid, alpha-tocopherol, glutathione, ubiquinone, ubiquinol, and cysteine). The predominant changes are in MDA, ascorbic acid, glutathione, cysteine, and cystine. The mitochondrial fraction of brain and liver showed oxidative changes as assayed by MDA similar to those of the tissue homogenate. Our results show that the responses of the brain to oxidative stress by acute or chronic exercise are quite different from those in the liver, heart, fast muscle, and slow muscle; oxidative stress by acute or chronic exercise elicits different responses depending on the organ tissue type and its endogenous antioxidant levels.

Animals↗
PubMed2000

Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism.

Mitochondria use energy derived from fuel combustion to create a proton electrochemical gradient across the mitochondrial inner membrane. This intermediate form of energy is then used by ATP synthase to synthesize ATP. Uncoupling protein-1 (UCP1) is a brown fat-specific mitochondrial inner membrane protein with proton transport activity. UCP1 catalyzes a highly regulated proton leak, converting energy stored within the mitochondrial proton electrochemical potential gradient to heat. This uncouples fuel oxidation from conversion of ADP to ATP. In rodents, UCP1 activity and brown fat contribute importantly to whole-body energy expenditure. Recently, two additional mitochondrial carriers with high similarity to UCP1 were molecularly cloned. In contrast to UCP1, UCP2 is expressed widely, and UCP3 is expressed preferentially in skeletal muscle. Biochemical studies indicate that UCP2 and UCP3, like UCP1, have uncoupling activity. While UCP1 is known to play an important role in regulating heat production during cold exposure, the biological functions of UCP2 and UCP3 are unknown. Possible functions include 1) control of adaptive thermogenesis in response to cold exposure and diet, 2) control of reactive oxygen species production by mitochondria, 3) regulation of ATP synthesis, and 4) regulation of fatty acid oxidation. This article will survey present knowledge regarding UCP1, UCP2, and UCP3, and review proposed functions for the two new uncoupling proteins.

Animals↗
PubMed2000

Ischemia after carotid endarterectomy: comparison between transcranial Doppler sonography and diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Hyperintense signals on diffusion-weighted MR images (DWIs) are believed to correspond accurately with cerebral ischemic events. Intraoperative transcranial Doppler sonography (TCD) can reveal hemodynamic and embolic events during carotid endarterectomy (CEA). Our purpose was to determine whether the occurrence of hyperintense signals on postoperative DWIs corresponds to intraoperative embolic or hemodynamic events. METHODS: Seventy-seven CEAs were monitored intraoperatively with TCD to record blood flow velocity changes after cross clamping to ascertain the presence of adequate collateral flow and to record microembolic signals. DWI was used to classify the hemisphere ipsilateral to the CEA by type: 0, no lesions (n = 51); I, cortical lesions only (n = 2); II, subcortical white matter lesions only (n = 6); III, mixed type with cortical and subcortical lesions (n = 11); IV, large territorial infarcts (n = 6); and V, other types of lesions (n = 1). RESULTS: Neither the five clinical events (one transient ischemic attack, two minor strokes, and two major strokes) nor any DWI type (I-V) showed a relationship to blood velocity decreases after cross clamping or, in patients who were selectively shunted, to total ischemic time necessary for shunt insertion and removal. Total microembolic signal count was significantly higher in the five CEAs with clinical events than in those without. It was also higher on the DWIs showing a hyperintense lesion as compared with DWIs showing no lesion. CONCLUSION: Apart from lesions corresponding to clinical deficits, CEA is associated with a substantial number of small areas of brain tissue at risk for irreversible ischemia. The main cause of intraoperative stroke seems to be embolism, suggesting that microembolic signals in CEA are highly relevant events for brain tissue.

Brain Ischemia↗
PubMed1999

Assessment of uncoupling activity of the human uncoupling protein 3 short form and three mutants of the uncoupling protein gene using a yeast heterologous expression system.

The human uncoupling protein 3 gene generates two mRNA transcripts, uncoupling protein 3L and uncoupling protein 3S, which are predicted to encode long and short forms of the uncoupling protein 3 protein, respectively. While uncoupling protein 3L is similar in length to the other known uncoupling proteins, uncoupling protein 3S lacks the last 37 C-terminal residues. A splice site mutation in the human uncoupling protein 3 gene, resulting in the exclusive expression of uncoupling protein 3S, and a number of point mutations in the uncoupling protein 3 gene have been described. This study compares the biochemical activity of uncoupling protein 3S as well as three mutants of the uncoupling protein 3 gene (V9M, V102I, R282C) with that of uncoupling protein 3L utilizing a yeast expression system. All proteins were expressed at similar levels and had qualitatively similar effects on parameters related to the uncoupling function. Both uncoupling protein 3S and uncoupling protein 3L decreased the yeast growth rate by 35 and 52%, increased the whole yeast basal O2 consumption by 26 and 48%, respectively, and decreased the mitochondrial membrane potential as measured in whole yeast by uptake of the fluorescent potential-sensitive dye 3'3-dihexyloxacarbocyanine iodide. In isolated mitochondria, uncoupling protein 3S and uncoupling protein 3L caused a similar (33 and 35%, respectively) increase in state 4 respiration, which was relatively small compared to uncoupling protein 1 (102% increase). A truncated version of uncoupling protein 3S, lacking the last three C-terminal residues, Tyr, Lys and Gly, that are part of a carrier motif that is highly conserved among all mitochondrial carriers, had a greatly reduced uncoupling activity. The two naturally occurring uncoupling protein 3 mutants, V9M and V102I, were similar to uncoupling protein 3L with respect to effects on the yeast growth and whole yeast O2 consumption. The R282C mutant had a reduced effect compared to uncoupling protein 3L. In summary, uncoupling protein 3S and the three mutants of uncoupling protein 3 appear to be functional proteins with biochemical activities similar to uncoupling protein 3L, although uncoupling protein 3S and the R282C mutant have a modestly reduced function.

Carrier Proteins↗
PubMed1999

Assessment of uncoupling activity of uncoupling protein 3 using a yeast heterologous expression system.

Uncoupling protein 3L, uncoupling protein 1 and the mitochondrial oxoglutarate carrier were expressed in Saccharomyces cerevisae. Effects on different parameters related to the energy expenditure were studied. Both uncoupling protein 3L and uncoupling protein 1 reduced the growth rate by 49% and 32% and increased the whole yeast O2 consumption by 31% and 19%, respectively. In isolated mitochondria, uncoupling protein 1 increased the state 4 respiration by 1.8-fold, while uncoupling protein 3L increased the state 4 respiration by 1.2-fold. Interestingly, mutant uncoupling protein 1 carrying the H145Q and H147N mutations, previously shown to markedly decrease the H+ transport activity of uncoupling protein 1 when assessed using a proteoliposome system (Bienengraeber et al. (1998) Biochem. 37, 3-8), uncoupled the mitochondrial respiration to almost the same degree as wild-type uncoupling protein 1. Thus, absence of this histidine pair in uncoupling protein 2 and uncoupling protein 3 does not by itself rule out the possibility that these carriers have an uncoupling function. The oxoglutarate carrier had no effect on any of the studied parameters. In summary, a discordance exists between the magnitude of effects of uncoupling protein 3L and uncoupling protein 1 in whole yeast versus isolated mitochondria, with uncoupling protein 3L having greater effects in whole yeast and a smaller effect on the state 4 respiration in isolated mitochondria. These findings suggest that uncoupling protein 3L, like uncoupling protein 1, has an uncoupling activity. However, the mechanism of action and/or regulation of the activity of uncoupling protein 3L is likely to be different.

Animals↗
PubMed1999

[Intracerebral hemorrhage in the context of amyloid angiopathy].

The purpose of our study was to evaluate the characteristic findings of acute hemorrhage due to amyloid angiopathy with computed tomography. 14 patients of intracranial hemorrhage with histologically confirmed cerebral amyloid angiopathy were observed over a period of 4 years. Characteristic findings were a lobar hemorrhage in superficial localisation, cortical involvement, subarachnoid hemorrhage, the multiplicity of hemorrhages and repeated episodes. Severe cerebral amyloid angiopathy is often accompanied by multiple petechial hemorrhages, restricted to a cortical-subcortical distribution, detectable by magnetic resonance imaging. These findings suggest that cerebral amyloid angiopathy is not a rare cause of atraumatic lobar hemorrhage. Amyloid angiopathy should be considered in any elderly patient with superficial intracerebral hemorrhage in an atypical location.

Aged↗
PubMed1999

Quantification of glutaric acid by isotope dilution mass spectrometry for patients with glutaric acidemia type I: selected ion monitoring vs. selected ion storage.

An isotope dilution mass spectrometric assay for the quantification of glutaric acid in urine and serum samples was developed. The performance of a quadrupole mass filter (QMF) gas chromatography-mass spectrometry (GC-MS) instrument, operated in the selected ion monitoring mode, and a quadrupole ion trap (QIT) GC/MS instrument, operated in the selected ion storage mode, was compared. Both instruments gave linear standard curves with glutaric acid concentrations between 0.19 and 3.8 microM. The average coefficients of correlation were 0.9998 and 0.9993 for the QMF and the QIT system, respectively. There was good agreement between the glutaric acid concentrations measured with the two instruments. The run-to-run precision was between 1.2 and 3.7% and between 6.2 and 8.6%, the average recovery of glutaric acid in urine and serum samples was 96 and 103% with the QMF and QIT instrument, respectively. We conclude that although the QMF has a slightly better performance, both instruments can be used to reliably measure glutaric acid concentrations from urine and serum patient samples.

Child↗
PubMed1999

A GC/MS/MS screening method for multiple organic acidemias from urine specimens.

A gas chromatography tandem mass spectrometry method using an ion trap GC/MS system was developed to quickly screen urine samples for 14 organic acids associated with multiple organic acidemias. The following organic acids are used as diagnostic markers: methylmalonic acid, glutaric acid, 2-ketoisocaproic acid, succinylacetone, 3-methylcrotonylglycine, tiglylglycine, isovalerylglycine, fumaric acid, butyrylglycine, propionylglycine, hexanoylglycine, adipic acid, suberic acid, and sebacic acid. 2-ketocaproic acid is used as an internal standard. The samples are prepared using a solid-phase extraction and converted to trimethylsilyl derivatives. The extraction efficiency for the 14 compounds is between 57 and 106%. A derivatized standard mixture of the 14 markers is run prior to the patient samples to determine the accurate absolute and relative retention times. The samples are then injected and the product ion spectra monitored. For data analysis, one characteristic product ion plot is extracted for each of the 14 marker compounds, and the presence of a peak with the expected retention time is determined. The areas of the product ion peaks are compared with the reference range determined from 30 normal controls. Ten samples of patients with known organic acidemias were measured. For all patients, diagnostic peaks at the expected retention times of at least five times the upper limit of the reference range were detected. The method, with its relatively fast sample preparation, short 10.0 min run time and simple data analysis, is suitable for use as a quick metabolic screen of very sick patients in whom there is concern regarding the possibility of a treatable inborn error.

Acids↗
PubMed1998

Periodate-oxidized ATP stimulates the permeability transition of rat liver mitochondria.

Periodate-oxidized ADP (oADP)2 and periodate-oxidized ATP (oATP) stimulate the permeability transition in energized rat liver mitochondria measured as the Ca2+-efflux induced by Ca2+ and Pi. In the presence of Mg2+ and Pi, mitochondria lose intramitochondrial adenine nucleotides at a slow rate. oATP induces a strong decrease of the matrix adenine nucleotides which is inhibited by carboxyatractyloside. Under these conditions, Mg2+ prevents the opening of the permeability transition pore. EGTA prevents the Pi-induced slow efflux of adenine nucleotides, but is without effect on the oATP-induced strong decrease of adenine nucleotides. This oATP-induced strong adenine nucleotide efflux is inhibited by ADP. oATP reduces the increase of matrix adenine nucleotides occurring when the mitochondria are incubated with Mg2+ and ATP. This effect of oATP is also prevented by carboxyatractyloside. oATP is not taken up by the mitochondria. It is suggested that oATP induces a strong efflux of matrix adenine nucleotides by the interaction with the ADP/ATP carrier from the cytosolic side. The induction of the mitochondrial permeability transition by oADP and oATP is attributed to two mechanisms-a strong decrease in the intramitochondrial adenine nucleotide content, especially that of ADP, and a stabilization of the c-conformation of the ADP/ATP carrier.

Adenine Nucleotides↗
PubMed1998

[Contribution of nuclear medicine to the diagnosis of recurrent brain tumors and cerebral radionecrosis].

The evaluation of brain tumor recurrence and therapy-induced benign changes following surgery and/or irradiation is a diagnostic challenge for imaging methods based on either morphology (cCT/MRI) or function (SPECT/PET). Current literature and the present data of our own patients demonstrate the diagnostic efficiency of IMT-SPECT and FDG-PET in the detection of recurrence and in-vivo grading. Thirty-nine patients suspected of brain tumor recurrence at follow-up were studied by FDG-PET and IMT-SPECT. Thirty-four of 39 patients showed recurrences; in 12 cases even a change in the grade of malignancy was observed. All high-grade recurrences could be confirmed by either methods. IMT-SPECT showed a higher sensitivity in detecting low-grade tumors at recurrence. In contrast to IMT-SPECT, FDG-PET supports sufficient in-vivo grading. Both methods can be used to differentiate between tumor recurrence and radionecrosis. In conclusion the results of our study demonstrate the efficiency of IMT-SPECT and FDG-PET in confirming recurrences and determining the actual tumor grade.

Adult↗
PubMed1998

Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study.

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.

Amino Acids↗
PubMed1998

Changes of cerebral perfusion after osmotherapy in acute cerebral edema assessed with perfusion weighted MRI.

Perfusion is thought to be impaired in brain edema due to reduced perfusion pressure. Brain edema therapy is assumed to improve perfusion. We assessed regional cerebral blood flow (rCBF), regional cerebral blood volume (rCBV) and mean transit time of blood (MTT) using perfusion-weighted magnetic resonance imaging (MRI) in 15 patients showing acute local brain edema due to infarction or intracerebral hematoma. Patients were treated by intravenous infusion of 125 ml 40% sorbitol over 10 min. rCBF, rCBV and MTT in the edematous region were measured before and 30 min after treatment. Before treatment rCBF (46.5 +/- 12.1 vs. 42.9 +/- 10.5 ml 100 g-1 min-1), MTT (4.7 +/- 1.9 vs. 4.0 +/- 1.7 s) and rCBV (5.4 +/- 1.7 vs. 4.7 +/- 1.1 ml 100 g-1) were significantly (p < 0.05) increased in the edematous region compared to the contralateral side. After treatment no significant differences could be found. We interpret the elevation of MTT and rCBV in the edema as signs of an autoregulative compensation of an impaired perfusion. rCBF is even over-compensated. After brain edema therapy perfusion seems normalised. This new MRI method appears as useful for measuring therapeutic effects on cerebral perfusion.

Aged↗
PubMed1998

Determination of serum physiological concentration of methylmalonic acid by gas chromatography-mass spectrometry with selected ion monitoring.

We developed a sensitive assay for the rapid determination of serum methylmalonic acid concentration using capillary gas chromatography-mass spectrometry (GC/MS) with selected ion monitoring and a simple solid-phase extraction. The assay was linear up to 10,000 nmol/L and had a detection limit < 50 nmol/L, average recovery of 98% and between-day coefficient of variation at concentrations of 570 and 2206 nmol/L of 7.7% and 5.4%, respectively (n = 25). Comparison with another validated GC/MS method using sera with a wide range of methylmalonic acid concentrations (94-2020 nmol/L) revealed a slope and intercept of 0.97 and 17 nmol/L, respectively (n = 38). Methylmalonic acid concentrations determined by this assay in a group of apparently healthy individuals ranged from 64-331 nmol/L (n = 81). We conclude that the method is ideally suited for the determination of methylmalonic acid at physiological concentrations in both clinical and research laboratories.

Biological Assay↗
PubMed1997

Detection and identification of NAD-catabolizing activities in rat tissue homogenates.

NAD may be degraded in several ways. A large number of investigations have shown that at least those catabolic routes which involve the formation of ADP-ribose are related to regulatory processes. In this study a rapid assay was utilized that permits identification of NAD-degrading enzymes directly in sodium dodecylsulfate polyacrylamide gels. Enzymatic activities were recovered by washing the gels in the presence of mild detergents such as lauryl dimethylamine N-oxide or Triton X-100. Subsequent incubation of the gels in the presence of the fluorescent analog 1,N6 etheno-NAD visualized NAD-degrading enzymes. Following excision of the fluorescent bands from the gels, the actual activity of the proteins was established by incubating the gel slices with 14C-labeled NAD and subsequent product analysis by thin layer chromatography (TLC). Homogenates from rat renal cortex and spleen were analyzed by this procedure. While in the spleen homogenate only a single band could be 'activity-stained', in the kidney three bands were detected. Kidney proteins with apparent molecular masses of about 210,000 and 105,000 Da were identified as phosphodiesterase and NAD pyrophosphatase (alkaline phosphodiesterase I), respectively. The third protein exhibited an apparent molecular mass of 41,000. The spleen protein (apparent molecular mass 45,000 Da) cleaved NAD to nicotinamide and ADP-ribose identifying it as NAD glycohydrolase. The procedure is suitable to screen for NAD-converting activities in crude extracts. It is specific for proteins which function as monomers or homo-oligomers.

Adenosine Diphosphate Ribose↗