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At least 1,639 records · Page 91Linked to original sources
PubMed1995

Frequency domain source localization shows state-dependent diazepam effects in 47-channel EEG.

The topic of this study was to evaluate state-dependent effects of diazepam on the frequency characteristics of 47-channel spontaneous EEG maps. A novel method, the FFT-Dipole-Approximation (Lehmann and Michel, 1990), was used to study effects on the strength and the topography of the maps in the different frequency bands. Map topography was characterized by the 3-dimensional location of the equivalent dipole source and map strength was defined as the spatial standard deviation (the Global Field Power) of the maps of each frequency point. The Global Field Power can be considered as a measure of the amount of energy produced by the system, while the source location gives an estimate of the center of gravity of all sources in the brain that were active at a certain frequency. State-dependency was studied by evaluating the drug effects before and after a continuous performance task of 25 min duration. Clear interactions between drug (diazepam vs. placebo) and time after drug intake (before and after the task) were found, especially in the inferior-superior location of the dipole sources. It supports the hypothesis that diazepam, like other drugs, has different effects on brain functions depending on the momentary functional state of the brain. In addition to the drug effects, clearly different source locations and Global Field Power were found for the different frequency bands, replicating earlier reports (Michel et al., 1992).

Acoustic Stimulation↗
PubMed1991

Evaluation of fingerprinting methods for identification of Helicobacter pylori strains.

Variation amongst strains of Helicobacter pylori was examined by 35S-methionine-labelled protein SDS-PAGE (Radio-PAGE), immunoblot and DNA fingerprinting techniques. These methods allowed discrimination amongst isolates and showed total correlation. Pig and baboon gastric Helicobacter pylori-like organisms were found to be very similar to Helicobacter pylori by both Radio-PAGE and immunoblotting, whereas a Helicobacter mustelae isolate was markedly different. The HindIII restriction endonuclease digest patterns of Helicobacter pylori DNA illustrated the considerable genomic variation of this organism. The Radio-PAGE and immunoblot typing methods both gave precise identification of Helicobacter pylori strains, but Radio-PAGE was found to give higher resolution and represents a standardised universally applicable fingerprinting method for Helicobacter pylori.

Animals↗
PubMed1992

Ordering of human chromosome 3p markers by radiation hybrid mapping.

To construct a panel of radiation hybrids (RHs) for human chromosome 3p mapping, mouse microcell hybrid cells, A9(neo3/t)-5, containing a single copy of human chromosome 3p with pSV2neo plasmid DNA integrated at 3p21-p22 were irradiated and fused to mouse A9 cells. A panel of 96 RHs that retain several sizes and portions of human chromosome 3p segments was used to map 25 DNA markers for chromosome 3p. Eight of them, H28, H29, H32, H33, H35, H38, H48, and H64, were cloned from Alu-primed PCR products using A9(neo3/t)-5 cell DNA as a template. The most likely order of the 24 markers, except for H28, based on the statistical ordering method proposed by Falk, was cen-D3S4-D3S3-D3S30-H29-D3S13-D3S2-+ ++H48-D3F15S2-D3S32-D3S23-CCK-H35-H33- D3S11-D3S12-RARB-THRB(ERBA2-pBH302)- H64-H38-RAF1-D3S18-H32-D3S22-pter. The order and location of these markers were in good agreement with those previously determined by other mapping methods, suggesting that a panel of these 96 RHs is a valuable source for a rapid mapping of human chromosome 3p markers.

Chromosome Mapping↗
PubMed2004

Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential.

The c-Jun N-terminal protein kinases (JNKs) form one subfamily of the mitogen-activated protein kinase (MAPK) group of serine/threonine protein kinases. The JNKs were first identified by their activation in response to a variety of extracellular stresses and their ability to phosphorylate the N-terminal transactivation domain of the transcription factor c-Jun. One approach to study the function of the JNKs has included in vivo gene knockouts of each of the three JNK genes. Whilst loss of either JNK1 or JNK2 alone appears to have no serious consequences, their combined knockout is embryonic lethal. In contrast, the loss of JNK3 is not embryonic lethal, but rather protects the adult brain from glutamate-induced excitotoxicity. This latter example has generated considerable enthusiasm with JNK3, considered an appropriate target for the treatment of diseases in which neuronal death should be prevented (e.g. stroke, Alzheimer's and Parkinson's diseases). More recently, these gene knockout animals have been used to demonstrate that JNK could provide a suitable target for the protection against obesity and diabetes and that JNKs may act as tumour suppressors. Considerable effort is being directed to the development of chemical inhibitors of the activators of JNKs (e.g. CEP-1347, an inhibitor of the MLK family of JNK pathway activators) or of the JNKs themselves (e.g. SP600125, a direct inhibitor of JNK activity). These most commonly used inhibitors have demonstrated efficacy for use in vivo, with the successful intervention to decrease brain damage in animal models (CEP-1347) or to ameliorate some of the symptoms of arthritis in other animal models (SP600125). Alternative peptide-based inhibitors of JNKs are now also in development. The possible identification of allosteric modifiers rather than direct ATP competitors could lead to inhibitors of unprecedented specificity and efficacy.

Amino Acid Sequence↗
PubMed2001

False positives and false negatives in genome scans.

It is emphasized that two types of errors are made in the testing of a hypothesis, false positive (type I) and false negative (type II). Genome-wide scans involving many markers give rise to the problem of multiple testing, which results in an increased number of false positives, thus necessitating a correction in the nominal significance level. While the literature has concentrated reasonably heavily on controlling false positives in genomic scans, the need to control false negatives has been largely neglected. This chapter highlights this need and attempts to strike a balance between the two error types. The need to develop alternative methods for discriminating between false positives and true positives is also stressed.

Chromosome Mapping↗
PubMed2000

Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1).

Phospholipase C-beta (PLC beta) catalyses the generation of inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate (IP(2)), a key step in the intracellular transduction of a large number of extracellular signals, including neurotransmitters and hormones modulating diverse developmental and functional aspects of the mammalian central nervous system. Four mammalian isozymes are known (PLC beta 1-4), which differ in their function and expression patterns in vivo. We have characterized the human PLC beta 1 genomic locus (PLC beta 1), cloned two distinct PLC beta 1 cDNAs (PLC beta 1a and b) and analysed their respective expression patterns in a comprehensive panel of human tissues using quantitative TaqMan technology. The two cDNAs derive from transcripts generated through alternative splicing at their 3' end, and are predicted to encode for PLC beta 1 isoforms differing at their carboxy-terminus. The human PLC beta 1 isoforms are co-expressed in the same tissues with a distinctly CNS-specific profile of expression. Quantitative differences in PLC beta 1 isoform expression levels are observed in some tissues. Transient expression of epitope-tagged versions of the two isoforms followed by immunofluorescence revealed localization of the proteins to the cytoplasm and the inner side of the cell membrane. Finally, we characterized the structure of the PLC beta 1 locus and confirmed its mapping to human chromosome 20.

Amino Acid Sequence↗
PubMed1995

Juvenile nasopharyngeal angiofibroma and familial adenomatous polyposis: an association?

Juvenile nasopharyngeal angiofibroma is a benign neoplasm affecting the nasopharynx of male adolescents. Two patients treated at Temple University Hospital for this condition were also diagnosed with familial adenomatous polyposis. Familial adenomatous polyposis results from the inheritance of a mutated adenomatous polyposis coli gene in an autosomal dominant pattern. The development of colorectal carcinoma in middle age is seen almost invariably in familial adenomatous polyposis, if a prophylactic colectomy is not performed. To identify a possible association between juvenile nasopharyngeal angiofibroma and familial adenomatous polyposis, chart reviews and patient interviews were carried out for all patients treated for juvenile nasopharyngeal angiofibroma at Temple University Hospital between 1985 and 1993. Single-strand conformational polymorphism was performed to detect the presence of certain adenomatous polyposis coli gene mutations within the germline DNA of those juvenile nasopharyngeal angiofibroma patients not previously found to have familial adenomatous polyposis. Although no more patients with both juvenile nasopharyngeal angiofibroma and familial adenomatous polyposis were found by these methods, the two patients with both disorders previously identified constitute 22% of our juvenile nasopharyngeal angiofibroma series. The implications of these findings are discussed.

Adenomatous Polyposis Coli↗
PubMed1985

[EEG mapping during a visuo-spatial task. Averaged maps and group statistics].

Twenty young volunteers (10 men, 10 women), righthanded, students, have been recorded in EEG cartography in different situations. We have compared the quantified EEGs when the subjects were resting, eyes closed and later, eyes opened, looking at a cartoon. The EEGs were quantified by spectral Fourier analysis and submitted to data reduction. Ten spectral parameters were computed, yielding 51 variables allowing computations and drawings of 90 EEG maps. Mean parameters, mean variables, averaged EEG maps have been computed for the entire group, between sub-groups, between hemispheres. Non-parametric permutation Fisher tests have been applied for statistical comparisons and statistical validations of the EEG maps computed between subjects. The activation of EEG tracings produced by the opening of the eyes were caracterized topographically by: mean alpha frequencies increased over temporal and rolandic areas; mean alpha amplitudes in microV divided by a factor 3 for occipital areas but unchanged in topography; mean relative amplitudes divided by a factor 2 but with a topography being more parietal than occipital for the alpha rhythm; a resonance coefficient greater over the left parietal than the right (alpha more regular), whereas it was greater over the right occipital than the left during the resting condition. Statistically for the whole group, the left hemisphere, recorded after the right, is more 'activated' in the eyes closed situation. During visual attention, the left hemisphere is less activated than the right.

Adult↗
PubMed1998

Substrate specificity of prostate-specific antigen (PSA).

BACKGROUND: The serine protease prostate-specific antigen (PSA) is a useful clinical marker for prostatic malignancy. PSA is a member of the kallikrein subgroup of the (chymo)trypsin serine protease family, but differs from the prototypical member of this subgroup, tissue kallikrein, in possessing a specificity more similar to that of chymotrypsin than trypsin. We report the use of two strategies, substrate phage display and iterative optimization of natural cleavage sites, to identify labile sequences for PSA cleavage. RESULTS: Iterative optimization and substrate phage display converged on the amino-acid sequence SS(Y/F)Y decreases S(G/S) as preferred subsite occupancy for PSA. These sequences were cleaved by PSA with catalytic efficiencies as high as 2200-3100 M-1 s-1, compared with values of 2-46 M-1 s-1 for peptides containing likely physiological target sequences of PSA from the protein semenogelin. Substrate residues that bind to secondary (non-S1) subsites have a critical role in defining labile substrates and can even cause otherwise disfavored amino acids to bind in the primary specificity (S1) pocket. CONCLUSION: The importance of secondary subsites in defining both the specificity and efficiency of cleavage suggests that substrate recognition by PSA is mediated by an extended binding site. Elucidation of preferred subsite occupancy allowed refinement of the structural model of PSA and should facilitate the development of more sensitive activity-based assays and the design of potent inhibitors.

Amino Acid Sequence↗
PubMed2003

Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses.

Pavlovian eyeblink conditioning is a useful model system for studying how the temporal relationship between a conditioned stimulus and an unconditioned stimulus is represented in the brain. As an example, the response topography formed under a complex conditioning paradigm, involving 2 randomly alternating interstimulus intervals (ISIs), manifests a conditioned response (CR) with 2 distinctive peaks that correspond to the 2 ISIs. The authors present the first full report of neuronal activities in the cerebellar interpositus nucleus of rabbits performing bimodal responses. All CR-related activities exhibited firing patterns that highly correlated with and preceded eyeblink responses. The striking similarity between the time course of bimodal CRs and neuronal responses indicates that neuronal activities in the cerebellum are causally related to the production of behavioral CRs.

Animals↗
PubMed1977

The pattern of loci on Drosophila chromosomes.

In this study, we have attempted to detect and describe patterns in the arrangement of gene loci within chromosomes of a metazoon. Known loci (842 of them) on the first three chromosomes of Drosophila melanogaster have been characterised according to a list of 45 properties and the distributions of these properties have been examined systematically. For all these properties, there is little, if any, evidence of clustering between known loci that are not close enough to belong to the same 10-locus group. Our analysis has, however, revealed evidence confirming that some properties show a tendency to cluster within a 10-locus group. Even this tendency is not strong, except for some of the morphological properties. However, it is apparently at variance with the findings of Elston and Glassman (1967), based on fewer data.

Animals↗
PubMed2001

A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome.

Hallervorden-Spatz syndrome (HSS) is an autosomal recessive neurodegenerative disorder associated with iron accumulation in the brain. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals iron deposits in the basal ganglia. In this respect, HSS may serve as a model for complex neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, Huntington disease and human immunodeficiency virus (HIV) encephalopathy, in which pathologic accumulation of iron in the brain is also observed. Thus, understanding the biochemical defect in HSS may provide key insights into the regulation of iron metabolism and its perturbation in this and other neurodegenerative diseases. Here we show that HSS is caused by a defect in a novel pantothenate kinase gene and propose a mechanism for oxidative stress in the pathophysiology of the disease.

Amino Acid Sequence↗
PubMed2003

Understanding neural system dynamics through task modulation and measurement of functional MRI amplitude, latency, and width.

Estimates of hemodynamic amplitude, delay, and width were combined to investigate system dynamics involved in lexical decision making. Subjects performed a lexical decision task using word and nonword stimuli rotated 0 degrees, 60 degrees, or 120 degrees. Averaged hemodynamic responses to repeated stimulation were fit to a Gamma-variate function convolved with a heavyside function of varying onset and duration to estimate each voxel's activation delay and width. Consistent with prolonged reaction times for the rotated stimuli and nonwords, the motor cortex showed delayed hemodynamic onset for both conditions. Language areas such as the lingual gyrus, middle temporal gyrus, fusiform gyrus, and precuneus all showed delayed hemodynamic onsets to rotated stimuli but not to nonword stimuli. The inferior frontal gyrus showed both increased onset latency for rotated stimuli and a wider hemodynamic response to nonwords, consistent with prolonged processing in this area during the lexical decision task. Phonological processing areas such as superior temporal and angular gyrus showed no delay or width difference for rotated stimuli. These results suggest that phonological routes but not semantic routes to the lexicon can proceed regardless of stimulus orientation. This study demonstrates the utility of estimating hemodynamic delay and width in addition to amplitude allowing for more quantitative measures of brain function such as mental chronometry.

Adult↗
PubMed2002

Chromosome 6.

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Chromosome Mapping↗