Biomedical subjects

J Schwarz

Publications and source records attributed to J Schwarz.

At least 73 records · Page 4Linked to original sources

PubMed2000

Polymer-supported carbene complexes of palladium: well-defined, air-stable, recyclable catalysts for the Heck reaction

N-Heterocyclic dicarbene chelate complexes of formula [cis-CH2N(H)C=C(H)N(R)C2PdX2] (X = Br, I; R = (CH2)nOH; n = 2, 3) have been prepared and structurally characterized (for X= I, n = 2). The complexes were immobilized on a functionalized polystyrene support (Wang resin) through one of the oxygen centres. The complexes efficiently catalyze the Heck reaction of activated and non-activated arylbromides, are recyclable under aerobic conditions and exhibit hardly any leaching, which is in line with our theoretical investigations on ligand dissociation energies related to Pd0 and PdII centres.

Journal Article↗

PubMed2000

1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism.

The endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline (salsolinol), which is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been reported to inhibit mitochondrial complex I (NADH-Q reductase) activity as does the MPTP metabolite 1-methyl-4-phenylpyridinium ion (MPP(+)). However, the mechanism of salsolinol leading to neuronal cell death is still unknown. Thus, we correlated indices of cellular energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to salsolinol and compared these results with data obtained with MPP(+). Both toxins induce time and dose-dependent decrease in cell survival with IC(50) values of 34 microM and 94 microM after 72 h for salsolinol and MPP(+), respectively. Furthermore, salsolinol and MPP(+) produce a decrease of intracellular net ATP content with IC(50) values of 62 microM and 66 microM after 48 h, respectively. In contrast to MPP(+), salsolinol does not induce an increase of intracellular net NADH content. In addition, enhancing glycolysis by adding D-glucose to the culture medium protects the cells against MPP(+) but not salsolinol induced cellular ATP depletion and cytotoxicity. These results suggest that cell death induced by salsolinol is due to impairment of cellular energy supply, caused in particular by inhibition of mitochondrial complex II (succinate-Q reductase), but not complex I.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis.

BACKGROUND: Specific binding to dopamine transporters may serve as a tool to detect early loss of nigrostriatal dopaminergic neurons in patients with Parkinson's disease. OBJECTIVE: To determine striatal dopamine transporter binding using the cocaine analogue [I-123]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chl orophenyl) tropane ([I-123]IPT) and single photon emission computed tomography. PATIENTS AND METHODS: We studied 9 control subjects (mean age, 58 years; range, 41-69 years) and 28 patients with early Parkinson's disease (Hoehn and Yahr stages I [n = 14] and II [n = 14] [symptom duration, <5 years]; mean age, 55.5 years; range, 36-71 years). Single photon emission computed tomography was performed 90 minutes after injection of 120 to 150 MBq of radioactive [I-123]IPT. RESULTS: Specific striatal [I-123] IPT binding (mean +/- SD) was significantly reduced in patients with early Parkinson's disease (ipsilateral striatum: 4.09+/-0.97; range, 2.46-6.40; contralateral striatum: 3.32+/-0.76; range, 1.80-5.13) compared with controls (left striatum: 7.28+/-0.94; range, 5.78-8.81; right striatum: 7.41+/-1.28; range, 5.58-9.44). IPT binding ratios (mean +/- SD) were significantly lower in patients with Hoehn and Yahr stage II (ipsilateral striatum: 3.47+/-0.75; contralateral striatum: 2.96+/-0.73) compared with those with Hoehn and Yahr stage I (ipsilateral striatum: 4.72+/-0.75; contralateral striatum: 3.69+/-0.61) (P<.001). The ipsilateral striatum of patients with Hoehn and Yahr stage I showed a significant mean+/-SD reduction of IPT binding (ipsilateral striatum: 4.72+/-0.75) compared with either right or left striatum of controls (P<.001). Only in 1 patient was IPT binding to the ipsilateral striatum (ratio, 6.40) higher than the lowest value observed in the striatum of a control subject (ratio, 5.58). CONCLUSIONS: Use of [I-123] IPT and single photon emission computed tomography demonstrates a reduction of dopamine transporter binding in patients with early Parkinson's disease. Significantly reduced IPT binding already observed in the ipsilateral striatum of patients with Hoehn and Yahr stage I demonstrates the potential of this method to detect preclinical disease.

Adult↗

PubMed2000

Development of miniaturized potentiometric nitrate- and ammonium selective electrodes for applications in water monitoring.

Mobile analysis with potentiometric sensors is well suited for field measurements. Ion-selective electrodes (ISE) based on polymeric membranes for in-situ determination of nitrate and ammonium contents in ground water, drinking water and surface water have been developed. The ISE are integrated in a multisensor module (MSM) for monitoring these ions over longer time intervals. The receptor is a PVC-membrane with tridodecylammonium nitrate (TDDA) for nitrate- and nonactine for ammonium-electrodes as ionophores. As plasticizer dibutylphthalate (DBT) was used. The main parameters for assessing the efficiency of these ISE are presented.

Journal Article↗

PubMed2000

Microarrayelectrodes for voltammetric and amperometric detection of organic pollutants.

Disk and band shaped microarrayelectrodes (MAE) of gold and carbon have been developed. These electrodes can be used for electrochemical detection of different organic pollutants in organic and aqueous media. Differential pulse voltammetric, cyclic voltammetric and amperometric investigations at these MAE in stationary and flowing solutions with selected pesticides, polyaromatic hydrocarbons (PAH) and phenols have been carried out.

Journal Article↗

PubMed2000

Mode dynamics of interacting neural populations by bi-orthogonal spectral decomposition.

A system of coupled bistable Hopf oscillators with an external periodic input source was used to model the ability of interacting neural populations to synchronize and desynchronize in response to variations of the input signal. We propose that, in biological systems, the settings of internal and external coupling strengths will affect the behaviour of the system to a greater degree than the input frequency. While input frequency and coupling strength were varied, the spatio-temporal dynamics of the network was examined by the bi-orthogonal decomposition technique. Within this method, effects of variation of input frequency and coupling strength were analyzed in terms of global, spatial and temporal mode entropy and energy, using the spatio-temporal data of the system. We observed a discontinuous evolution of spatio-temporal patterns depending sensitively on both the input frequency and the internal and external coupling strengths of the network.

Animals↗

PubMed2000

6-Hydroxydopamine toxicity towards human SH-SY5Y dopaminergic neuroblastoma cells: independent of mitochondrial energy metabolism.

6-Hydroxydopamine (6-OHDA) is widely used to generate animal models of Parkinson's disease. However, little is known about the intracellular events leading to cell death of dopaminergic neurones. Here we correlate indices of energy production and cell viability in human dopaminergic neuroblastoma SH-SY5Y cells after exposure to 6-OHDA. The toxin induces a time and dose-dependent decrease in cell survival with an IC50 value of 25 microM after 24 h. In contrast to the mitochondrial complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+), 6-OHDA-induced reduction of cell viability is not associated with a decrease of intracellular ATP content, intracellular ATP/ADP ratio or NAD+ content. In addition, preventing or forcing glycolysis do not alter 6-OHDA toxicity. The antioxidant D-alpha-tocopherol can attenuate cell death induced by 6-OHDA. These results suggest that cell death induced by 6-OHDA is not due to an inhibition of mitochondrial energy supply, but probably involves production of free radicals.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Protective effects of riluzole on dopamine neurons: involvement of oxidative stress and cellular energy metabolism.

Riluzole is neuroprotective in patients with amyotrophic lateral sclerosis and may also protect dopamine (DA) neurons in Parkinson's disease. We examined the neuroprotective potential of riluzole on DA neurons using primary rat mesencephalic cultures and human dopaminergic neuroblastoma SH-SY5Y cells. Riluzole (up to 10 microM:) alone affected neither the survival of DA neurons in primary cultures nor the growth of SH-SY5Y cells after up to 72 h. Riluzole (1-10 microM:) dose-dependently reduced DA cell loss caused by exposure to MPP(+) in both types of cultures. These protective effects were accompanied by a dose-dependent decrease of intracellular ATP depletion caused by MPP(+) (30-300 microM:) in SH-SY5Y cells without affecting intracellular net NADH content, suggesting a reduction of cellular ATP consumption rather than normalization of mitochondrial ATP production. Riluzole (1-10 microM:) also attenuated oxidative injury in both cell types induced by exposure to L-DOPA and 6-hydroxydopamine, respectively. Consistent with its antioxidative effects, riluzole reduced lipid peroxidation induced by Fe(3+) and L-DOPA in primary mesencephalic cultures. Riluzole (10 microM) did not alter high-affinity uptake of either DA or MPP(+). However, in the same cell systems, riluzole induced neuronal and glial cell death with concentrations higher than those needed for maximal protective effects (> or =100 microM:). These data demonstrate that riluzole has protective effects on DA neurons in vitro against neuronal injuries induced by (a) impairment of cellular energy metabolism and/or (b) oxidative stress. These results provide further impetus to explore the neuroprotective potential of riluzole in Parkinson's disease.

1-Methyl-4-phenylpyridinium↗

PubMed2000

Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson's disease and controls.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by complex behaviour during REM sleep. The aetiology of this disorder is still unknown, but a recent study showed an association between RBD and Parkinson's disease. We therefore studied striatal postsynaptic dopamine D2 receptor density with [123I](S)-2-hydroxy-3-iodo-6-methoxy-(1-ethyl-2-pyrrolidinylmethyl ) benzamide ([123I]IBZM) and the striatal presynaptic dopamine transporter with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorop henyl) tropane ([123I]IPT) using single-photon emission computed tomography (SPECT) in patients with idiopathic RBD. We compared the [123I]IPT-SPECT results of five patients with polysomnographically confirmed idiopathic RBD with the [123I]IPT-SPECTs of seven age- and sex-matched controls without a history of sleep disorders, and of 14 patients with Parkinson's disease (Hoehn and Yahr stage I). All RBD patients had significantly reduced striatal [123I]IPT binding compared with the controls (RBD: right, 2.94 +/- 0.32, left, 3.03 +/- 0.41; controls: right, 4.41 +/- 0.17, left, 4.34 +/- 0.21; P = 0.003), but significantly higher striatal [123I]IPT binding compared with the striatum contralateral to the symptomatic body side of the Parkinson's disease patients (Parkinson's disease: ipsilateral, 3.17 +/- 0.36, P = 0.298; contralateral, 2.51 +/- 0.31, P = 0.019). Uptake of [123I]IBZM was not significantly different in the RBD group compared with the controls. This study demonstrates that [123I]IPT-SPECT is a useful diagnostic tool in RBD and that reduced striatal dopamine transporters may be a pathophysiological mechanism of idiopathic RBD. (Results are given as mean +/- standard deviation.)

Adult↗

PubMed2000

Public health surveillance of hepatitis C: can it identify incident cases?

OBJECTIVES: To evaluate a follow-up system to identify incident cases among individuals notified with the hepatitis C virus (HCV). METHOD: A cross-sectional survey of medical practitioners treating individuals notified to the NSW Health Department as having HCV between August 1996 and August 1997 was conducted. RESULTS: Five hundred and fifty-four new notifications were received during the study period (70.7 per 100,000 people). Ninety-six per cent of notifications were followed up with 54 individuals (9.7%) identified as incident cases. Incident cases were significantly younger than prevalent cases (median age 30 vs. 39, p < 0.001) with drug and alcohol notifications being more likely to be incident cases. CONCLUSION: HCV transmission is continuing at relatively high levels with incident cases being significantly younger than prevalent cases. IMPLICATIONS: An efficient notification follow-up strategy that identifies incident cases could be routinely used to assess the effectiveness of population-based initiatives aimed at reducing HCV transmission.

Adult↗

PubMed2000

Catechol-O-methyltransferase inhibition attenuates levodopa toxicity in mesencephalic dopamine neurons.

Inhibition of catechol-O-methyltransferase (COMT; EC 2.1.1.6) is a new therapeutic strategy in the treatment of Parkinson's disease. However, nothing is known about the effects of COMT inhibition on levodopa (L-dopa)-induced toxicity in dopamine (DA) neurons. Therefore we evaluated the effects of the selective COMT inhibitors Ro 41-0960, OR-486, and tolcapone alone and in combination with L-dopa in primary mesencephalic cultures from rat. Neither COMT inhibitor affected the growth of tyrosine hydroxylase immunoreactive (THir) cells with concentrations up to 10 microM when studied alone. However, Ro 41-0960 reduced the L-dopa-induced THir cell loss after 24 h in a dose-dependent manner, shifting the TD(50) value from 21 microM in the absence to 71 microM in the presence of 1 microM Ro 41-0960 (P <.01) without affecting survival of non-DA neurons. OR-486 and the clinically used COMT inhibitor tolcapone showed similar effects. In contrast, toxicity induced by D-dopa was not altered by COMT inhibitors. Furthermore, the primary metabolite of L-dopa formed by COMT, 3-O-methyldopa, and the methyl group donor S-adenosyl-L-methionine used by COMT did not alter THir neuron survival and L-dopa-induced toxicity, respectively, with concentrations up to 100 microM. These data demonstrate that COMT inhibition attenuates L-dopa toxicity toward DA neurons in vitro, but probably not by preventing 3-O-methyldopa production or cellular S-adenosyl-L-methionine depletion.

Animals↗

PubMed2000

Malignant peripheral nerve sheath tumors in the setting of segmental neurofibromatosis. Case report.

Approximately 100 cases of segmental neurofibromatosis (NF5) have been reported in the recent literature. Patients with NF5 present with café-au-lait macules, freckles, and/or neurofibromas limited to one or adjacent dermatomes. Neurofibromas arising in NF5 have been uniformly considered to be benign; patients were thought to have an excellent prognosis without the risk of developing malignant peripheral nerve sheath tumors (PNSTs), which are characteristic in patients with the generalized form of this disease, von Recklinghausen's NF. In this report the authors detail the first observations of malignant PNSTs in two patients with NF5. Indications for surgical removal of a neurofibroma in a patient with NF include pain. neurological impairment, compression of adjacent structures, cosmetic disfigurement, and rapid tumor growth suggestive of malignant degeneration. Surgical indications are similar for patients with NF5. All patients with neurofibromas should be considered at risk for malignant degeneration.

Adult↗

PubMed2000

Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group.

OBJECTIVE: To evaluate whether visual assessment of [123I]-FP-CIT (DaTSCAN, Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism and essential tremor (ET). METHODS: [123I]-FP-CIT SPECT imaging was conducted in a six-center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken. RESULTS: The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection. CONCLUSION: Visual assessment of [123I]-FP-CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic-rigid syndrome.

Adult↗

PubMed1999

International Arctic Seas Assessment Project.

The International Atomic Energy Agency responded to the news that the former Soviet Union had dumped radioactive wastes in the shallow waters of the Arctic Seas, by launching the International Arctic Seas Assessment Project in 1993. The project had two objectives: to assess the risks to human health and to the environment associated with the radioactive wastes dumped in the Kara and Barents Seas; and to examine possible remedial actions related to the dumped wastes and to advise on whether they are necessary and justified. The current radiological situation in the Arctic waters was examined to assess whether there is any evidence for releases from the dumped waste. Potential future releases from the dumped wastes were predicted, concentrating on the high-level waste objects containing the major part of the radionuclide inventory of the wastes. Environmental transport of released radionuclides was modelled and the associated radiological impact on humans and the biota was assessed. The feasibility, costs and benefits of possible remedial measures applied to a selected high-level waste object were examined. Releases from identified dumped objects were found to be small and localised to the immediate vicinity of the dumping sites. Projected future annual doses to members of the public in typical local population groups were very small, less than 1 microSv--corresponding to a trivial risk. Projected future doses to a hypothetical group of military personnel patrolling the foreshore of the fjords in which wastes have been dumped were higher, up to 4 mSv/year, which still is of the same order as the average annual natural background dose. Moreover, since any of the proposed remedial actions were estimated to cost several million US$ to implement, remediation was not considered justified on the basis of potentially removing a collective dose of 10 man Sv. Doses calculated to marine fauna were insignificant, orders of magnitude below those at which detrimental effects on fauna populations might be expected to occur. Remediation was thus concluded not to be warranted on radiological grounds.

Animals↗

PubMed1999

The combination of hypointense and hyperintense signal changes on T2-weighted magnetic resonance imaging sequences: a specific marker of multiple system atrophy?

OBJECTIVE: To compare the frequency and specificity of hypointense magnetic resonance imaging (MRI) signal changes alone with the frequency and specificity of a pathological MRI pattern consisting of a hyperintense lateral rim and a dorsolateral signal attenuation on T2-weighted MRIs in patients with parkinsonism of various origins. PATIENTS: Ninety patients with Parkinson disease (PD) (n = 65), progressive supranuclear palsy (PSP) (n = 10), and multiple system atrophy (MSA) of the striatonigral degeneration type (n = 15) underwent MRI. SETTING: University medical center. RESULTS: Nine of the 15 patients with MSA showed the pattern with hyperintense lateral rim and a dorsolateral hypointense signal attenuation on T2-weighted images within the putamen. This pattern was not found in the 65 patients with PD, nor in the 10 patients with PSP. Only hypointense changes in the putamen were found in 6 patients (9%) with PD, 4 patients (40%) with PSP, and 5 patients (36%) with MSA. CONCLUSIONS: Our data suggest that the pattern consisting of hypointense and hyperintense T2 changes within the putamen is a highly specific MRI sign of MSA, while hypointensity alone remains a sensitive, but nonspecific MRI sign of MSA. In clinically doubtful cases, the appearance of a hypointense and hyperintense signal pattern on MRI makes the diagnosis of PD very unlikely, while hypointense signal changes alone do not exclude idiopathic PD.

Aged↗

PubMed1999

FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation.

Recently, mutations in the tau gene on chromosome 17 were found causative for autosomal dominantly inherited frontotemporal dementia and parkinsonism (FTDP-17). We describe a family carrying a missense mutation at nucleotide 1137 C --> T, resulting in the amino acid substitution P301S. Methods of investigations include clinical, electrophysiological, and imaging techniques. This kindred presents with a novel phenotype characterized by an early onset of rapidly progressive frontotemporal dementia and parkinsonism in combination with epileptic seizures. We define the dopaminergic deficits as being predominantly presynaptic by the use of single-photon emission computed tomography with a dopamine transporter ligand. The association of this early-onset phenotype with P301S mutation is not entirely consistent with current criteria for the diagnosis of frontotemporal dementias and may encourage the search for tau mutations in diseases similar but not identical to FTDP-17. Also, the change from proline to serine suggests that this mutation might contribute to tau hyperphosphorylation.

Adult↗

PubMed1999

INAA and PIXE of atmospheric and combustion aerosols.

Using instrumental neutron activation analyses and photon-induced x-ray emission techniques for analysis of size-fractionated atmospheric and combustion aerosols and other emission samples arising from fluidized-bed combustion of North Bohemian lignites up to 42 elements were determined in all samples types. This allowed the evaluation of element enrichment, time trends, and inter-element correlations and the performance of factor analysis of various fractions of atmospheric aerosols. The data obtained on mass and element size distributions of aerosols and emission samples obtained upon lignite combustion in an experimental scale atmospheric fluidized-bed combustor without and with added hydrated lime and limestone were used to elucidate the mechanism of abatement of toxic trace and matrix elements from flue gas.

Aerosols↗

PubMed1999

Matrix effects in PIXE analysis of aerosols and ashes.

A comparison of instrumental neutron activation analysis (INAA) and proton-induced X-ray emission (PIXE) results for size-fractionated atmospheric aerosols ("coarse" and "fine" fractions with an equivalent aerodynamic diameter of 2-10 microns and < 2 microns, respectively, or the PM10 fraction) showed that PIXE yielded significantly lower results for the PM10 and coarse fractions, especially for elements with a low Z resulting from a particle size effect. Somewhat lower PIXE results were also obtained for the fine fraction of atmospheric aerosols. A correction is also needed for irregularly shaped deposits of combustion aerosols collected by a cascade impactor in 11 size fractions ranging from 0.016 to 14.3 microns, as well as for thick samples of fly and bottom ashes. An equivalent layer thickness (ELT) model is proposed to correct the matrix effects in PIXE. The approaches for the calculation of ELT using a comparison of PIXE and INAA results or by comparing PIXE results obtained using two different incident proton beam energies (1.31 and 2.35 MeV) are described. The correction for the ash pellets and irregular deposits are also discussed.

Aerosols↗