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Biomedical subjects

C Humphries

Publications and source records attributed to C Humphries.

At least 19 recordsLinked to original sources
PubMed2000

Removing electroencephalographic artifacts by blind source separation.

Eye movements, eye blinks, cardiac signals, muscle noise, and line noise present serious problems for electroencephalographic (EEG) interpretation and analysis when rejecting contaminated EEG segments results in an unacceptable data loss. Many methods have been proposed to remove artifacts from EEG recordings, especially those arising from eye movements and blinks. Often regression in the time or frequency domain is performed on parallel EEG and electrooculographic (EOG) recordings to derive parameters characterizing the appearance and spread of EOG artifacts in the EEG channels. Because EEG and ocular activity mix bidirectionally, regressing out eye artifacts inevitably involves subtracting relevant EEG signals from each record as well. Regression methods become even more problematic when a good regressing channel is not available for each artifact source, as in the case of muscle artifacts. Use of principal component analysis (PCA) has been proposed to remove eye artifacts from multichannel EEG. However, PCA cannot completely separate eye artifacts from brain signals, especially when they have comparable amplitudes. Here, we propose a new and generally applicable method for removing a wide variety of artifacts from EEG records based on blind source separation by independent component analysis (ICA). Our results on EEG data collected from normal and autistic subjects show that ICA can effectively detect, separate, and remove contamination from a wide variety of artifactual sources in EEG records with results comparing favorably with those obtained using regression and PCA methods. ICA can also be used to analyze blink-related brain activity.

Artifacts↗
PubMed1999

Spatially fixed patterns account for the spike and wave features in absence seizures.

Despite genetic, morphological and experimental in vivo, data implying fixed abnormalities in patients with absence seizures, attempts to find highly consistent features in the 3-Hz spike-and-wave pattern recorded during sequential seizures from the same subject have been largely unsuccessful. We used a new data decomposition technique called Independent Component Analysis (ICA) to separate multiple spike-and-wave episodes in the EEG recorded from five subjects with absence seizures into multiple consistent components. Each component corresponded to a temporally-independent waveform and a fixed spatial distribution. Almost all components separated by the ICA algorithm had overlapping, largely frontal spatial distributions. The analysis unmasked 5-8 components from each subject that were consistently activated across all seizures, with no components detected that were selectively activated by one seizure and not another. The "spike" and "wave" features noted in the EEG of every subject were each separated by the ICA algorithm into two or more components. Other components were active only at the beginning of each seizure or were related to ongoing brain activity not directly related to the 3Hz spike-and-wave pattern. By contrast randomly selected spatial patterns used for data decomposition resulted in components that were uninformative, similar to simply changing the montage for viewing the EEG. Our results suggest that despite previously described variability in the raw EEG, certain highly specific spatial distributions of activation are reproducible across seizures. These may reflect ictal and non-ictal brain activity consistently activating the same group of neurons.

Action Potentials↗
PubMed1998

A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.

Slow- and fast-twitch myofibers of adult skeletal muscles express unique sets of muscle-specific genes, and these distinctive programs of gene expression are controlled by variations in motor neuron activity. It is well established that, as a consequence of more frequent neural stimulation, slow fibers maintain higher levels of intracellular free calcium than fast fibers, but the mechanisms by which calcium may function as a messenger linking nerve activity to changes in gene expression in skeletal muscle have been unknown. Here, fiber-type-specific gene expression in skeletal muscles is shown to be controlled by a signaling pathway that involves calcineurin, a cyclosporin-sensitive, calcium-regulated serine/threonine phosphatase. Activation of calcineurin in skeletal myocytes selectively up-regulates slow-fiber-specific gene promoters. Conversely, inhibition of calcineurin activity by administration of cyclosporin A to intact animals promotes slow-to-fast fiber transformation. Transcriptional activation of slow-fiber-specific transcription appears to be mediated by a combinatorial mechanism involving proteins of the NFAT and MEF2 families. These results identify a molecular mechanism by which different patterns of motor nerve activity promote selective changes in gene expression to establish the specialized characteristics of slow and fast myofibers.

3T3 Cells↗
PubMed1998

A new method for detecting state changes in the EEG: exploratory application to sleep data.

A new statistical method is described for detecting state changes in the electroencephalogram (EEG), based on the ongoing relationships between electrode voltages at different scalp locations. An EEG sleep recording from one NREM-REM sleep cycle from a healthy subject was used for exploratory analysis. A dimensionless function defined at discrete times ti, u(ti), was calculated by determining the log-likelihood of observing all scalp electrode voltages under the assumption that the data can be modeled by linear combinations of stationary relationships between derivations. The u(ti), calculated by using independent component analysis, provided a sensitive, but non-specific measure of changes in the global pattern of the EEG. In stage 2, abrupt increases in u(ti) corresponded to sleep spindles. In stages 3 and 4, low frequency (approximately equal to 0.6 Hz) oscillations occurred in u(ti) which may correspond to slow oscillations described in cellular recordings and the EEG of sleeping cats. In stage 4 sleep, additional irregular very low frequency (approximately equal to 0.05-0.2 Hz) oscillations were observed in u(ti) consistent with possible cyclic changes in cerebral blood flow or changes of vigilance and muscle tone. These preliminary results suggest that the new method can detect subtle changes in the overall pattern of the EEG without the necessity of making tenuous assumptions about stationarity.

Electroencephalography↗
PubMed1997

Pilot study of HLA alloimmunization after transfusion with pre-storage leucodepleted blood products in aplastic anaemia.

We have performed a pilot study to examine the incidence of alloimmunization using pre-storage leucocyte-depleted blood products (PLDP) in 16 previously transfused aplastic anaemia (AA) patients with no detectable HLA antibodies. A further eight AA patients with HLA antibodies received HLA-matched PLDP. Leucodepleted apheresed platelets were obtained using either Cobe spectra or Haemonetics system with an integral pall filter. Pall BPF4 filters were used for red cell preparation. Patients' sera were tested for HLA antibodies using lymphocytotoxicity (LCT). Patients who were HLA antibody negative by LCT at study entry were further tested with enzyme-linked immunoassay (ELISA). Out of 16 patients, two (12%) formed anti-HLA antibodies with a median follow-up of 9 months (range 1-15), but did not display platelet refractoriness to random donor platelets. Two patients were inadvertently transfused with non-leucodepleted blood products when later referred back to their local hospital. Both subsequently demonstrated HLA antibodies by LCT and became platelet refractory. These results contrast with a 50% incidence of HLA alloimmunization in a control group of AA patients transfused prior to this study with non-PLDP. HLA antibodies could no longer be detected by LCT in follow-up of three out of eight patients with HLA antibodies at study entry. Only one patient experienced non-haemolytic febrile transfusion reactions (NHFTR). We conclude that PLDP reduce the risk of alloimmunization even in previously transfused AA patients, PLDP are associated with a low incidence of NHFTR, and all new AA patients should receive PLDP from diagnosis.

Adolescent↗
PubMed1996

NMDA receptor mRNA correlation with antemortem cognitive impairment in schizophrenia.

We investigated the expression of the N-methyl-D-aspartate (NMDA) receptor, an important glutamate receptor, in brains from a population of well characterized schizophrenic patients who prospectively consented to tissue donation. Levels of NR-1 mRNA in tissue homogenates of superior temporal cortex were reduced by 30% in cognitively impaired schizophrenic patients compared with controls (p < 0.04), while levels in patients without cognitive impairment showed no such reduction. The NR-1 mRNA deficit was significantly correlated with general cognitive function as rated with the Global Deterioration scale (p < 0.001), the Mini-Mental State examination (p < 0.01) and the premorbid IQ determined using the National Adult Reading Test (NART, p < 0.01). NR-1 mRNA concentration was not correlated with age, sex, pH or postmortem delay in the control and schizophrenia group when analysed separately or combined. There was, therefore, a significant correlation between NR-1 mRNA loss and cognitive deterioration in patients with schizophrenia.

Adult↗
PubMed1995

Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia.

No consistent markers of pathology have been established yet in schizophrenia, although abnormalities in frontal and temporal structures are indicated from positron emission tomography (PET) studies. We have used in situ hybridization to investigate functional changes focusing on the quantitation of cholecystokinin (CCK) mRNA, whose product has been shown to be depleted in schizophrenia. CCK mRNA and G(o) alpha-subunit mRNA were measured in eight schizophrenic and eight control subjects matched for age and postmortem delay. The study revealed a marked decrease in CCK mRNA of 83% in frontal cortex (BA10) and 63% in superior temporal cortex (BA22) in schizophrenia with no change in G(o) alpha-subunit mRNA in either region. This study was extended to a further series of eight patients to determine the reproducibility of this effect and to quantitate laminar changes in CCK mRNA. Quantitation of CCK mRNA in inner cortical layers (layer V/VI) was carried out in frontal and temporal cortex in comparison with G(o) alpha-subunit mRNA, which is also concentrated in this region; this study showed a similar selective decrease in CCK mRNA in frontal and temporal cortex of 47% and 51%, respectively. A confirmatory decrease in CCK mRNA was also obtained by slot blot analysis of CCK mRNA in tissue extracts of frontal cortex by reference to levels of beta-tubulin mRNA, CCK mRNA:beta-tubulin mRNA was significantly decreased (67%) in schizophrenic tissue compared to control tissue. There was no significant correlation of CCK mRNA loss with neuroleptic treatment or duration of illness.

Adult↗
PubMed1992

Extensive and selective mutation of a rearranged VH5 gene in human B cell chronic lymphocytic leukemia.

B cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have few and apparently random mutations. However, in this study, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03% in B-CLLs whereas the somatic mutation levels are much lower in CD5+ and CD5- cord B cells, adult peripheral blood B cells, and Epstein-Barr virus-transformed CD5+ B cell lines (0.45, 0.93, and 1.92%, respectively). Complementary determining region 1 (CDR1) mutation in CLLs is particularly prevalent, and interchanges in CDRs often lead to acquisition of charge. Analysis of somatic mutations and mutations to charged residues demonstrated that the mutations in CLLs are highly selected.

Adult↗
PubMed1992

Analysis of VH251 gene mutation in chronic lymphocytic leukemia (CLL) and normal B-cell subsets.

B-cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have low and random mutations. In this study, however, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03%, and there is a high ratio of replacement to silent mutation in CDRs relative to FWRs. CDR1 mutation is particularly prevalent, and interchanges often lead to acquisition of charge. In VH251 rearranged in CD5+ and CD5- cord-blood B cells, adult peripheral-blood B cells and EBV-transformed CD5+ B-cell lines, the somatic mutation levels are much lower (0.45%, 0.93%, and 1.92%, respectively) with concomitantly lower replacement to silent ratios in CDRs relative to FWRs. The extensive and highly selective somatic mutation of VH251 used in CD5+ CLL cells strongly suggests that part of CLL is generated under the influence of antigen selection and stimulation.

B-Lymphocyte Subsets↗
PubMed1991

Nasal resonometer: an instrument for the assessment and treatment of hypernasality.

We describe an instrument which enables the measurement of the ratio of nasal to oral sound pressures to be made during normal speech. The technique incorporates a novel phase locking technique which effectively discriminates the spectral characteristic of resonant peaks occurring during nasalized speech from other nasal emissions. The results enable an assessment of the degree of resonance in real time, the trend of diagnostic measurements within a treatment session and the success achieved in reaching targets set during treatment.

Adolescent↗
PubMed1987

Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia.

We have identified a family of human immunoglobulin heavy-chain variable-region (VH) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged VH genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged VH genes (VHTS1 and VHWS1) that were 90% homologous. The corresponding germ-line gene, VH251, was found to be part of a small (four gene) VH gene family, which we term VHV. The DNA sequence homology to VHWS1 (95%) and VHTS1 (88%) and identical restriction sites on the 5' side of VH confirm that rearrangement of VH251 followed by somatic mutation produced the identical VH gene rearrangements in the two siblings. VHTS1 is not a functional VH gene; a functional VH rearrangement was found on the other chromosome of this patient. The other two siblings had different VH gene rearrangements. All used different diversity genes. Mechanisms proposed for non-random selection of a single VH gene include developmental regulation of this VH gene rearrangement or selection of a subpopulation of B cells in which this VH has been rearranged.

Amino Acid Sequence↗
PubMed1983

Cognitive characteristics of the type A coronary-prone behavior pattern.

Recent findings indicate that Type As attend more to tasks defined as central, and less to tasks defined as peripheral, than do Type Bs. If this A-B difference in allocation of attention occurs naturally, as well as in response to experimental instructions, it would have implications for other phenomena, such as the process of creating a category from a series of perceptual events. It was reasoned that across a series of acquisition stimuli, Type As, compared to Type Bs, would be more responsive to the development of central tendencies in the frequency of appearance of the attributes that comprise the stimuli. That is, Type As should be more attentive to frequently occurring attributes (by virtue of their centrality in the evolving category definition) and less attentive to rarely occurring attributes. This difference in attention should lead to a difference in encoding. On a subsequent recognition-memory task, then, Type As should report with greater certainty than Type Bs that they had seen stimuli composed of frequently observed attributes and should report with greater certainty that they had not seen stimuli composed of rarely observed attributes. In a test of this reasoning, students classified as As and Bs completed a concept-formation and recognition-memory task under one of four levels of situational challenge. The predicted patterns occurred among subjects in whom moderate and high levels of challenge had been induced. The findings thus support the arguments that As and Bs process information differently and that this processing difference must be elicited by situational challenge.

Attention↗
PubMed1969

Effect of pH changes on the cardiac sphincter.

In 16 normal subjects the pressure characteristics of the cardiac sphincter have been examined. The effect of perfusing the gastric aspect of the sphincter mucosa has been studied by comparing the effects of saline with those of solutions where pH ranged from 1.0 to 8.0. Acid perfusion produced an increase in sphincteric pressure, particularly at pH 3.0. This suggests that a physiological mechanism exists which can increase the barrier pressure to gastrooesophageal reflux during periods of active secretion of the stomach, as occurs in digestion.

Atropine↗
PubMed1969

Action of gastrin on the lower oesophageal sphincter in man.

Both hog gastrin and synthetic gastrin stimulate the cardiac sphincter to increase tone and augment the resistance to reflux. Endogenous gastrin has a similar effect, and gastrin also stimulates the secretion of acid which has also been found to increase the resistance of the sphincter, but the effect of gastrin appears to be independent of the secretory stimulus.

Cardia↗