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R M Chapman

Publications and source records attributed to R M Chapman.

At least 19 recordsLinked to original sources
PubMed1999

Dysregulation of cyclin dependent kinase 6 expression in splenic marginal zone lymphoma through chromosome 7q translocations.

The increased or inappropriate expression of genes with oncogenic properties through specific chromosome translocations is an important event in the pathogenesis of B-cell lymphoproliferative diseases. Recent studies have found deletions or translocations of chromosome 7q to be the most common cytogenetic abnormality observed in SLVL, a leukemic variant of SMZL, with the q21-q22 region being most frequently affected. In three patients with translocations between chromosomes 2 and 7, the cloning of the breakpoints at 7q21 revealed that each was located within a small region of DNA 3.6 kb upstream of the transcription start site of cyclin dependent kinase 6 (CDK6). In each case the translocation event was consistent with aberrant VJ recombination between the immunoglobulin light chain region (Ig kappa) on chromosome 2p12 and DNA sequences at 7q21, resembling the heptamer recombination site. The t(7;21) breakpoint in an additional patient with splenic marginal zone lymphoma (SMZL), resided 66 kb telomeric to the t(2;7) breakpoints juxtaposing CDK6 to an uncharacterized transcript. In two of the SLVL patient samples, the CDK6 protein was found to be markedly over expressed. These results suggest that dysregulation of CDK6 gene expression contributes to the pathogenesis of SLVL and SMZL.

Aged↗
PubMed1998

Detailed molecular delineation of 13q14.3 loss in B-cell chronic lymphocytic leukemia.

A region of chromosome 13q14.3, telomeric to the Retinoblastoma gene RB-1 is frequently deleted in patients with B-cell chronic lymphocytic leukemia (B-CLL). A cosmid and P1-derived artificial chromosome (PAC) contig spanning over 600 kb has been constructed, which encompasses this locus. The contig clones have been used to order a number of markers along the minimally deleted region and to localize a series of CpG islands corresponding to possible candidate genes. A novel polymorphic dinucleotide repeat, 6E3.2, present in one of the ordered cosmid clones has been isolated for use in deletion mapping studies of patient DNA. Leukemic samples from 229 CLL patients have been screened for loss of heterozygosity using microsatellite markers and analyzed for hemizygous and homozygous deletions by Southern blot techniques using genomic probes selected from cosmids across the region. Hemizygous deletions were found in 31% of cases with an additional 10% showing homozygous loss. The use of these probes has defined the commonly deleted area to less than 130 kb, centromeric to the locus D13S272.

Chromosomes, Artificial, Yeast↗
PubMed1997

Absolute pitch and sex effect event-related potential activity for a melodic interval discrimination task.

Absolute pitch is a special ability which allows for special perceptual/cognitive strategies. Studies have shown differences in event-related scalp potentials between absolute-pitch (AP) and relative-pitch (RP) subjects of equal musical training. In this study, highly trained musicians (15 females/15 males) performed a melodic interval discrimination task, using intervals on-pitch in equal-tempered tuning (A4 = 440 Hz) and tuned a half-semitone sharp. Subjects identified target intervals (probability 0.2) in a series of 400 randomly transposed intervals. AP subjects were expected to perform differently across intonation conditions, whereas RP subjects were not. Event-related potentials (ERPs) were recorded from three midline sites and two lateral sites. ERPs were analyzed by principal component analysis of variance. Sex was also considered as an independent subject variable. Performance was not significantly different either by absolute pitch or sex. Reaction times did not reveal any significant interactions involving AP or sex, but showed a significant effect by response type (target/nontarget). Strong P3 activity appeared to the target melodic intervals regardless of subject group or intonation. PCA factors with maxima at 352, 511, and 709 ms were sensitive to task relevance. Males showed greater positivity than females along the midline. A significant intonation by response type by sex interaction indicated a greater spread of values for females than males, and greater similarity in response by sex for the sharp than the on-pitch intervals. AP subjects showed reduced P3 activity along the midline, but increased over lateral sites. In a difficult musical task, the ERPs were sensitive to the sex of the listeners, as well as to whether they had absolute pitch.

Acoustic Stimulation↗
PubMed1996

Sex differences in memory for timbre: an event-related potential study.

Although female/male cognitive differences have been studied for some time, little is known about such differences relative to music. Highly-trained musicians (15 females and 15 males) performed a memory task for musical timbre modeled after the missing-displaced visual object test known to favor female performance. Subjects were tested on memory for a timbre missing from a previously presented set of synthesized instrumental timbres, and a control series of white noise bursts at two different intensity levels. Subjects were given the missing-displaced visual object test and ERPs were recorded from three midline sites and two lateral sites. Waveforms were subjected to a principal component analysis and analysis of variance. Females and males performed equally well on both of the auditory series and the visual object test. Both auditory series elicited several ERP components: a strong early peak to the white noise, and both early (P3a) and late (P3b) peaks to the timbre series. PCA factor, maximum at 675 ms (P3b), showed a main effect for sex across both series with males > females. PCA factor, maximum at 336 ms (P3a), showed larger Fz to Pz differential for females than males for both auditory series. Females show a greater differentiation between targets and nontargets in the white noise series, suggesting greater sensitivity to changes in intensity. Interactions involving absolute pitch also appeared in the sensory processing time frames. Although the behavioral measures did not show significant sex differences, the ERP measures did show reliable task-related sex differences.

Adult↗
PubMed1996

PCR analysis of polymorphisms at the D13S25 locus.

Evidence that the D13S25 locus lies close to a potential tumour suppressor gene implicated in the pathogenesis of B-CLL has been based on detection of LOH and bi-allelic loss using the pH2-42 probe. The SspI polymorphism detected by this probe has been identified by sequencing adjacent clones and a polymorphic (TA)n repeat has been found. Amplification of the region encompassing both polymorphic markers by PCR increases the informativity to 80%.

Alleles↗
PubMed1995

EP component identification and measurement by principal components analysis.

Between the acquisition of Evoked Potential (EP) data and their interpretation lies a major problem: What to measure? An approach to this kind of problem is outlined here in terms of Principal Components Analysis (PCA). An important second theme is that experimental manipulation is important to functional interpretation. It would be desirable to have a system of EP measurement with the following characteristics: (1) represent the data in a concise, parsimonous way; (2) determine EP components from the data without assuming in advance any particular waveforms for the components; (3) extract components which are independent of each other; (4) measure the amounts (contributions) of various components in observed EPs; (5) use measures that have greater reliability than measures at any single time point or peak; and (6) identify and measure components that overlap in time. PCA has these desirable characteristics. Simulations are illustrated. PCA's beauty also has some warts that are discussed. In addition to discussing the usual two-mode model of PCA, an extension of PCA to a three-mode model is described that provides separate parameters for (1) waveforms over time, (2) coefficients for spatial distribution, and (3) scores telling the amount of each component in each EP. PCA is compared with more traditional approaches. Some biophysical considerations are briefly discussed. Choices to be made in applying PCA are considered. Other issues include misallocation of variance, overlapping components, validation, and latency changes.

Brain↗
PubMed1994

Frequent homozygous deletions of the D13S25 locus in chromosome region 13q14 defines the location of a gene critical in leukaemogenesis in chronic B-cell lymphocytic leukaemia.

Cytogenetic studies of B-cell chronic lymphocytic leukaemia show structural abnormalities involving the 13q14 chromosome region as the only karyotypic change in a significant proportion of tumours. This observation suggests the location of a gene important in leukaemogenesis. A series of 68 BCLL tumours have been analysed for allele loss using a series of probes from 13q14. Using intragenic polymorphic markers from the retinoblastoma predisposition gene LOH was observed in 25% of tumours including 3/6 showing cytogenetically obvious deletions of the 13q14 region and 3/6 showing translocations involving 13q14. However, three deletions with proximal breakpoints in 13q14 did not show allele loss, demonstrating that the breakpoint lay distal to RB1. Using the D13S25 locus, which lies 1.6 cM distal to RB1, allele loss was seen in 90% of tumours with structural rearrangements of 13q14 and 75% of tumours with an apparently normal karyotype. 50% of these tumours showed homozygous loss of D13S25, suggesting that a 'tumour suppressor gene' lies in this region. The more distal D13S31 locus, 1 cM distal to D13S25, was infrequently involved in allele loss demonstrating that the minimum region of overlap for homozygous deletions is approximately 1 Mbp around the D13S25 locus.

Alleles↗
PubMed1993

Word meaningfulness and event-related potentials during phrase processing.

Evoked Potentials (EP) were recorded to visual presentation of words in phrases. Three EP components, P250, N400, P560, and their dependence on the role that each word plays in the phrase were studied. Subjects were requested to perform a congruity/incongruity task after the presentation of short phrases of two-types that differed in the position of meaningful keywords. We show how these keywords contribute substantially to N400 and possibly to P560 but do not reliably affect P250.

Adolescent↗
PubMed1990

Neuromagnetic topography of photoconvulsive response in man.

The neuromagnetic method was applied to the study of photoconvulsive responses. The identification of specific magnetic field distributions over the scalp was achieved by; (a) a stimulation paradigm consisting of series of trains of flicker stimuli randomly presented to the epileptic patient, after eye closure, to get epileptic responses while avoiding seizures; (b) a novel procedure for data analysis, to select consistent responses. These patterns, when sufficiently stable in time and dipolar in shape, were used for source localization in the usual biomagnetic framework of the equivalent current dipole source representation. The results of this approach suggest that different specific cortical areas are repeatedly and randomly activated, involving mainly the frontal, occipital and temporal areas, often with a hemispheric prevalence.

Brain↗
PubMed1989

Evoked potentials and the study of sentence comprehension.

Evoked brain potentials were used to monitor moment-by-moment decisions during language comprehension. Subjects read sentences containing temporary syntactic ambiguities for which one of the possible interpretations was semantically implausible. The N400 component of the evoked potential, which is sensitive to implausibility, was used to discover when during a sentence subjects made a decision about the ambiguity. The results demonstrate that readers try to interpret a syntactic ambiguity early in a sentence rather than waiting for disambiguating information. This introduces a new way to use brain activity to study sentence comprehension processes.

Decision Making↗
PubMed1989

A simple method for 3-dimensional localization of epileptic activity recorded by simultaneous EEG and MEG.

A simple method is presented to average target patterns in the magnetoencephalographic trace of epileptic activity by finding markers in an EEG channel. This method proves to be useful even in cases of low magnetic signal-to-noise ratio. After simultaneously recording electric and magnetic activity the user chooses in the electric trace a template of interest and determines within the same trace all the time points at which the EEG pattern is highly correlated with the chosen template. The magnetic trace portions recorded at those times are averaged together, extracting in this way the magnetic signal from the noise. The MEG results are applied to localize in the brain the active sources that contribute to the recorded signals.

Electroencephalography↗
PubMed1989

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Health Promotion↗
PubMed1984

Selective localization of alpha brain activity with neuromagnetic measurements.

A method of localizing brain activity by a new combination of magnetic and electrical recording, relative covariance, is described. The successful application of this method to alpha EEG is reported. Spontaneous human brain activity was recorded simultaneously with fixed scalp electrodes and a movable magnetometer. The analysis was restricted to the alpha rhythm, which was selected by a narrow bandpass filter centered at the observed alpha frequency. For each magnetometer location, the ratio of the covariance of the magnetic and electric signals to the electric variance was calculated, producing a map reflecting the magnetic field pattern. Clear maxima of opposite polarity over the left and right parietotemporal areas indicate bilateral current source areas near the midline, in the vicinity of the calcarine fissure, at a depth of 4-6 cm from the scalp. This relative covariance method may prove generally useful in localizing bioelectrical sources such as spontaneous brain rhythms.

Adult↗