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Biomedical subjects

C Klein

Publications and source records attributed to C Klein.

At least 109 records · Page 6Linked to original sources

Developmental functions for saccadic eye movement parameters derived from pro- and antisaccade tasks.

The few studies on the development of oculomotor functions conducted so far suggest strong developmental effects of age on different parameters of saccade control in childhood and adolescence. The present study aimed at determining developmental functions for a set of 22 parameters derivable from the examination of pro- and antisaccades elicited under the 200-ms gap and overlap conditions (100 trials under each of the four conditions). The statistical analyses (including multiple regression, analysis of covariance, and principal components analysis (PCA) were based on a sample of 199 subjects aged 6-28 years, including 66% males and 34% females. We obtained the following main results: (1) In most cases, the variable "age(-1)" predicted the dependent variables much better than age. (2) Multiple regression approaches using Age and Age(-1) as predictors accounted for 0-51% of the criterion variances, these values (adjusted R2) being large for the proportion of direction errors during the antisaccade tasks (0.46-0.51), medium for anti- (0.36-0.46) and prosaccadic (0.23-0.34) reaction times (RT) and their standard deviations (0.26-0.45), and negligible for the proportion of express saccades. (3) The age variables (particularly Age(-1)), furthermore, predicted some of the effects of the experimental task manipulations on the different dependent variables (e.g. the augmentation of direction errors under the gap as compared to the overlap condition of the antisaccade task) significantly. (4) PCA results suggest 5 factors of saccade control in this sample: 2 factors comprising the antisaccade parameters, 2 factors comprising the prosaccade parameters, and 1 factor comprising the anticipations. The best correlations of the age variables with the corresponding factor scores were obtained for the 2 factors related to the antisaccade task parameters.

Adolescent↗

[Comparison of various parameters for determining an index of myocardial perfusion reserve in detecting coronary stenosis with cardiovascular magnetic resonance tomography].

For the assessment of myocardial perfusion with cardiac magnetic resonance imaging, different semiquantitative parameters of the first pass signal intensity time curves can be calculated and myocardial perfusion reserve indices can be determined. In this study we evaluated the feasibility of different perfusion parameters and their perfusion reserve indices for the detection of significant coronary artery stenosis. The signal intensity time curves of the first pass of a gadolinium-DTPA bolus injected via a central vein catheter before and after dipyridamole infusion were investigated in 15 patients with single vessel (stenosis > or = 75% area reduction) and five patients without significant coronary artery disease. For the distinction of ischemic and nonischemic myocardial segments, semiquantitative parameters, such as maximal signal intensity, contrast appearance time, time to maximal signal intensity and the steepness of the signal intensity curve's upslope determined by a linear fit, were assessed after correction for the input function. For each parameter a myocardial perfusion reserve index was calculated and cut off values for the detection of significant coronary stenosis were defined. The diagnostic accuracy of each parameter was then examined prospectively in 36 patients with coronary artery disease and compared with coronary angiography. Where as a distinction of ischemic and normal myocardium was possible with myocardial perfusion reserve indices, semiquantitative parameters at rest or after vasodilation alone did not allow such a distinction. The perfusion reserve index calculated from the upslope showed the most significant difference between ischemic and nonischemic myocardial segments (1.19 +/- 0.4 and 2.38 +/- 0.45, p < 0.001) followed by maximum signal intensity, time to maximum signal intensity and contrast apperance time. Sensitivity, specificity and diagnostic accuracy was 87, 82 and 85% for the detection of hypoperfusion induced by significant coronary artery stenoses using the perfusion reserve index calculated from the upslope. The steepness of the first pass signal intensity curve's upslope, determined by a linear fit, is a feasible parameter for the detection of significant coronary artery disease with MR. Based on a myocardial perfusion reserve index of this parameter, ischemic myocardium can be identified with high diagnostic accuracy.

Adult↗

[The role of magnetic resonance imaging in the diagnosis of coronary disease].

As the number of diagnostic coronary angiographies without subsequent revascularization procedures is continuously rising, the need for non-invasive diagnostic procedures with a high diagnostic accuracy is well appreciated. Because of the technical advances in magnetic resonance imaging (MRI) over the last few years, major improvements have been made in the functional assessment of wall motion, myocardial perfusion and coronary flow measurements, as well as the visualization of the anatomy of the coronary arteries by MRI. Besides these classical parameters of ischemia and anatomical pathology, for the first time MRI might offer the possibility to not only non-invasively assess the lumen of the coronary arteries, but also to visualize the vessel wall. Thus, early manifestations of coronary artery disease may be detectable for the identification of patients with preclinical disease as candidates for aggressive risk modification. In this review the current status as well as future perspectives of MRI are discussed.

Angioplasty, Balloon, Coronary↗

Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkinsonism.

Dystonia is a movement disorder involving sustained muscle contractions and abnormal posturing with a strong hereditary predisposition and without a distinct neuropathology. In this study the TOR1A (DYT1) gene was screened for mutations in cases of early onset dystonia and early onset parkinsonism (EOP), which frequently presents with dystonic symptoms. In a screen of 40 patients, we identified three variations, none of which occurred in EOP patients. Two infrequent intronic single base pair (bp) changes of unknown consequences were found in a dystonia patient and the mother of an EOP patient. An 18-bp deletion (Phe323_Tyr328del) in the TOR1A gene was found in a patient with early onset dystonia and myoclonic features. This deletion would remove 6 amino acids close to the carboxy terminus, including a putative phosphorylation site of torsinA. This 18-bp deletion is the first additional mutation, beyond the GAG-deletion (Glu302/303del), to be found in the TOR1A gene, and is associated with a distinct type of early onset dystonia.

Adolescent↗

Spot compliant neuronal networks by structure optimized micro-contact printing.

Neuronal cell growth in vitro can be controlled with micropatterned structures of extracellular matrix proteins such as laminin. This technique is a powerful tool for studying neuronal cell function in order to increase experimental reproducibility and to specifically design innovative experimental setups. In this paper the correlation between the structural dimensions of the ECM pattern and the shape of the resulting cellular network is analyzed. The aim of the present study was to position neuronal cell bodies as precisely as possible and to induce directed cell differentiation. PCC7-MzN cells were cultured on laminin patterns. The line width, node size and gap size in-between cell adhesion sites was varied systematically. Micrographs of the samples were taken and statistically analyzed using Student's t-test and linear correlation methods. Precise cell positioning has successfully been performed and evidence for controlled neuronal polarization has been found. With a structure geometry of 4 microm line width, 20 microm node size and 10 microm gap size a nodal compliance of 86% (+/- 10%) has been achieved.

Animals↗

Gender differences in problem severity at assessment and treatment retention.

Women in treatment for substance abuse have been reported to have more severe problems at assessment than men but not to differ in treatment retention. To examine gender differences in problems at assessment, 30-day retention, and treatment completion, data from Detroit's publicly funded substance abuse treatment system were used. Women had significantly more severe problems at assessment, lower 30-day retention, and lower treatment completion rates than men. These gender differences in retention remained significant even after controlling for problem severity, primary drug of abuse, and referred treatment setting. There was no evidence of improvements in women's problems at assessment or retention over time during this period. Women presented with more severe problems at assessment and were less likely to stay in treatment for 30 days or to complete treatment than men. Monitoring gender differences in problems at presentation and retention outcomes is recommended to assess local need for interventions.

Adult↗

N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.

The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.

Actins↗

Different types of repeat expansion in the TATA-binding protein gene are associated with a new form of inherited ataxia.

A novel neurological syndrome has recently been described to be associated with an expanded polyglutamine domain. The expansion results from partial duplication within the TATA-binding protein (TBP). By investigation of 604 sporadic and familial cases with various forms of neurological syndromes and 157 unaffected individuals, we found repeat expansions in the TBP in four patients of two families with autosomal dominant inheritance of ataxia, dystonia, and intellectual decline. Two different genotypes for the repetitive sequence could be demonstrated which led to elongated polyglutamine stretches between 50 and 55 residues, whereas normal alleles with 27 to a maximum of 44 glutamine residues were found in this study. The expansion to 50 or more glutamine residues results in a pathological phenotype and confirms the report of a new polyglutamine disease.

Adult↗

Nitric oxide regulates adenylyl cyclase activity in rat striatal membranes.

The regulation of adenylyl cyclase activity by nitric oxide (NO) was studied in rat (Sprague-Dawley) striatal membranes. Three chemically distinct NO donors attenuated forskolin-stimulated activity but did not alter basal activity. Maximum inhibition resulted in a 50% decrease in forskolin-stimulated activity, consistent with the presence of multiple isoforms of adenylyl cyclase and our previous findings that only the forskolin-stimulated activity of the type-5 and -6 isoform family of enzymes is inhibited by NO. To monitor primarily the type-5 isoform, we examined the ability of NO donors to attenuate D(1)-agonist-stimulated adenylyl cyclase activity. Under those conditions, complete inhibition was observed. The data indicate that NO attenuates neuromodulator-stimulated cAMP signaling in the striatum.

Adenylyl Cyclases↗

Electroencephalographic abnormalities in aseptic meningitis and noninfectious headache. A comparative study.

BACKGROUND: The finding of abnormalities on electroencephalogram (EEG) during the course of aseptic meningitis is often considered to be indicative of parenchymal brain involvement, even in absence of clinical signs of encephalitis. OBJECTIVE: To investigate if patients with aseptic nonherpetic meningitis who have abnormal EEG recordings during the acute stage of the disease differ in clinical characteristics or cerebrospinal fluid findings from patients with aseptic meningitis and normal EEG recordings. METHODS: The EEG records of 82 patients with aseptic meningitis were reviewed. A comparative group consisted of 41 age-matched patients with severe headaches without evidence of meningeal inflammation. RESULTS: Significantly more patients with aseptic meningitis (28%) demonstrated abnormalities on EEG than controls (12%) (P =.048). Patients with aseptic meningitis and abnormal EEG findings (n = 23) did not differ in age, duration of symptoms, clinical course, cerebrospinal fluid cell count, or protein level from those with normal EEG findings (n = 59). However, all patients with aseptic meningitis who were confused (n = 5) also revealed EEG abnormalities (P<.00012). Patients with headache with normal EEG recordings did not differ from those with abnormal EEGs in age, sex, or duration of symptoms. Nevertheless, patients with common migraine (n = 9) showed abnormalities on EEG (P =.06) more frequently. CONCLUSIONS: The finding of an abnormal EEG in patients with aseptic meningitis, clear mental state and absence of focal neurological signs should not be used as proof of encephalitis. Because pathological examination is usually not performed, it remains unclear if EEG abnormalities in patients with aseptic meningitis indicate a silent parenchymal inflammation, or reflect an infectious encephalopathy.

Acute Disease↗

Analysis of respiratory mechanics by impulse oscillometry in non-sedated and diazepam-sedated swine.

Analysis of respiratory mechanics using impulse oscillometry is applicable to sedated, or non-sedated (trained) pigs when they are fixed in a sling. In this study, the influence of the following sources of variability on measurement results was examined: (i) sedation with diazepam; (ii) body weight of animals (ranging in age: 40 to 102 days); and (iii) time of the measurement (circadian influences). The following parameters were examined: respiratory rate (RR), tidal volume (v(t)), spectral resistance, reactance and coherence, each at 5, 10, 15 and 20 Hz (R5,...R20, X5,...X20, CO5...CO20, respectively), distal respiratory resistance (Rdist), and proximal airway resistance (Rprox). After sedation (using 1.5 mg diazepam per kg body weight), RR and v(t) decreased significantly. There was a significant improvement of CO5, CO10 and CO15. Increase in body weight was strongly correlated to v(t), furthermore to spectral resistance parameters. Impulse oscillometry system (IOS) parameters showed only slight non-significant alterations in dependency on the time of day. In consequence, different sources of variability must be taken into account when performing IOS measurements in swine.

Age Factors↗

umuDC-dnaQ Interaction and its implications for cell cycle regulation and SOS mutagenesis in Escherichia coli.

The Escherichia coli SOS-regulated umuDC gene products participate in a DNA damage checkpoint control and in translesion DNA synthesis. Specific interactions involving the UmuD and UmuD' proteins, both encoded by the umuD gene, and components of the replicative DNA polymerase, Pol III, appear to be important for regulating these two biological activities of the umuDC gene products. Here we show that overproduction of the epsilon proofreading subunit of Pol III suppresses the cold sensitivity normally associated with overexpression of the umuDC gene products. Our results suggest that this suppression is attributable to specific interactions between UmuD or UmuD' and the C-terminal domain of epsilon.

Bacterial Proteins↗

Calmodulin distribution and the actomyosin cytoskeleton in Toxoplasma gondii.

The gliding motility of the protozoan parasite Toxoplasma gondii and its invasion of cells are powered by an actin-myosin motor. We have studied the spatial distribution and relationship between these two cytoskeleton proteins and calmodulin (CaM), the Ca(2+)-dependent protein involved in invasion by T. gondii. A 3D reconstruction using labeling and tomographic studies showed that actin was present as a V-like structure in the conoidal part of the parasite. The myosin distribution overlapped that of actin, and CaM was concentrated at the center of the apical pole. We demonstrated that the actomyosin network, CaM, and myosin light-chain kinases are confined to the apical pole of the T. gondii tachyzoite. MLCK could act as an intermediate molecule between CaM and the cytoskeleton proteins. We have developed a model of the organization of the actomyosin-CaM complex and the steps of a signaling pathway for parasite motility.

Actins↗

Positron emission tomographic analysis of the nigrostriatal dopaminergic system in familial parkinsonism associated with mutations in the parkin gene.

A kindred from South Tyrol (northern Italy) with familial, adult-onset parkinsonism of pseudo-dominant inheritance and mutations in the parkin gene was recently described. To gain insight into basal ganglia dysfunction in this form of hereditary parkinsonism, positron emission tomography (PET) with 18-fluorodopa (FDOPA) and 11C-raclopride (RAC) was performed in 5 affected family members and 5 asymptomatic relatives with proven compound heterozygous or heterozygous parkin mutations. Results were compared to findings in healthy control subjects and patients with typical sporadic, idiopathic Parkinson's disease. Similar to findings in the sporadic Parkinson's disease group, presynaptic striatal FDOPA storage was decreased in patients with compound heterozygous parkin mutations, with the most prominent reduction in the posterior part of the putamen. Along with the presynaptic lowered FDOPA uptake, we found a uniform reduction of the striatal 11C-raclopride binding index in all affected family members as compared to asymptomatic family members carrying a heterozygous parkin mutation, sporadic Parkinson's disease, and control subjects. Our PET data provide evidence that parkinsonism in this family is associated with presynaptic dopaminergic dysfunction similar to idiopathic Parkinson's disease pathophysiology, along with alterations at the postsynaptic D2 receptor level. In asymptomatic carriers of a single parkin mutation with an apparently normal allele, we found a mild but statistically significant decrease of mean FDOPA uptake compared to control subjects in all striatal regions. These data indicate a preclinical disease process in these subjects.

Adult↗

Development of prosaccade and antisaccade task performance in participants aged 6 to 26 years.

There are few studies on the development of oculomotor functions during childhood. B. Fischer, M. Biscaldi, and S. Gezeck (1997) reported improvement of antisaccade task performance between ages 6 and 16 years. The present study is a replication and extension of those results. In three age groups (6-7, 10-11, 18-26 years), saccades during pro- and antisaccade tasks with 200-ms gap and overlap and during a fixation task were measured. Adults exhibited faster saccades and less prosaccades during the antisaccade tasks than 10-11-year-old children; these two groups had faster saccades during all tasks and less prosaccades during the anti- and the fixation task than 6-7-year-old subjects. Both children groups made more express saccades than adults. Results suggest different degrees of age-related improvement for different saccadic parameters, the effects being greatest for prosaccade inhibition during the antisaccade task and in line with the assumed protracted development of prefrontal functions.

Adolescent↗

Four-week test-retest stability of individual differences in the saccadic CNV, two saccadic task parameters, and selected neuropsychological tests.

The aim of the present study was the comparative assessment of the 4-week test-retest stabilities of the saccadic CNV (sCNV) and saccadic reaction times (SRT) during the execution of pro- and antisaccades, as well as the stability of RT during execution of two neuropsychological tests of alertness and S-R incompatibility. Prosaccades were elicited under the 200-ms gap and overlap conditions, antisaccades under the overlap condition (64 trials each). The EEG was recorded from 25 channels with a DC amplifier (MES, Munich). Data of 20 healthy participants were statistically analyzed. We found high test-retest correlations for all SRT (.76 < or = r(tt) < or = .88) and neuropsychological (.62 < or = r(tt) < or = .88) measures. For the sCNV, coefficients ranging between .58 (pro/gap) and .77 (anti/overlap) were obtained. Whereas SRT were significantly faster during the second than during the first session, group means for the saccadic CNV were stable across the sessions. Our results suggest high 4-week stability of individual differences in SRT, and moderate to good stabilities of saccadic CNV amplitudes. Our results recommend these "traitlike" measures to be used in individual differences research.

Adolescent↗