Biomedical subjects

S A Stevenson

Publications and source records attributed to S A Stevenson.

5 recordsLinked to original sources

PubMed2006

Altered gene expression in mice selected for high maternal aggression.

We previously applied selective breeding on outbred mice to increase maternal aggression (maternal defense). In this study, we compared gene expression within a continuous region of the central nervous system (CNS) involved in maternal aggression (hypothalamus and preoptic regions) between lactating selected (S) and nonselected control (C) mice (n= 6 per group). Using microarrays representing over 40,000 genes or expressed sequence tags, two statistical algorithms were used to identify significant differences in gene expression: robust multiarray and the probe logarithmic intensity error method. Approximately 200 genes were identified as significant using an intersection from both techniques. A subset of genes was examined for confirmation by real-time polymerase chain reaction (PCR). Significant decreases were found in S mice for neurotensin and neuropeptide Y receptor Y2 (both confirmed by PCR). Significant increases were found in S mice for neuronal nitric oxide synthase (confirmed by PCR), the K+ channel subunit, Kcna1 (confirmed by PCR), corticotrophin releasing factor binding protein (just above significance using PCR; P= 0.051) and GABA A receptor subunit 1A (not confirmed by PCR, but similar direction). S mice also exhibited significantly higher levels of the neurotransmitter receptor, adenosine A1 receptor and the transcription factors, c-Fos, and Egr-1. Interestingly, for 24 genes related to metabolism, all were significantly elevated in S mice, suggesting altered metabolism in these mice. Together, this study provides a list of candidate genes (some previously implicated in maternal aggression and some novel) that may play an important role in the production of this behavior.

Aggression↗

PubMed1998

Co-localization of dystrophin and beta-dystroglycan demonstrated in en face view by double immunogold labeling of freeze-fractured skeletal muscle.

An absence of dystrophin causes Duchenne muscular dystrophy, but the precise mechanism underlying necrosis of the muscle cells is still unclear. Dystrophin and beta-dystroglycan are components of a complex of at least nine proteins, the dystrophin-glycoprotein complex (DGC), that links the membrane cytoskeleton to extracellular elements in skeletal and cardiac muscle. Biochemical studies indicate that dystrophin is bound to other components of the DGC via beta-dystroglycan, which suggests that the distribution of these two proteins should be almost identical. In this study, therefore, we examined the spatial relationship between dystrophin and beta-dystroglycan with a range of different imaging techniques to investigate the extent of the predicted co-localization. We used (a) double immunogold fracture-label, a freeze-fracture cytochemical technique that allows high-resolution face-on views of labeled membrane components in thin sections and in platinum-carbon replicas, (b) double immunogold labeling of cryosections and (c) confocal microscopy. Both dystrophin and beta-dystroglycan were found over the entire fiber surface and, when labeled singly, the nearest neighbor spacing of labeling sites for the two proteins was indistinguishable. With double labeling, very close co-localization could be demonstrated. The results support the conclusion that dystrophin and beta-dystroglycan directly interact at the muscle plasma membrane. (J Histochem Cytochem 46:945-953, 1998)

Animals↗

PubMed1997

Analysis of the intraventricular electrogram for differentiation of distinct monomorphic ventricular arrhythmias.

This study investigated the effectiveness of correlation waveform analysis for identifying different ventricular electrogram morphologies of multiple VTs in the same patient. Patients with implantable antitachycardia devices are commonly subject to the occurrence of more than one distinct monomorphic VT. Each of these VTs may have unique therapeutic alternatives for termination. VTs with identical and different monomorphic configurations were recorded (1-500 Hz) using distal bipolar (1 cm) and distal unipolar electrograms from the right ventricular apex. Thirty-six distinct monomorphic VTs induced in 15 patients were analyzed. Nine VTs with identical morphologies (12/12 surface ECGs) were induced twice and used as a control. A template was created for each VT induced. Correlation waveform analysis was used to compare each depolarization of all other VTs induced subsequently in the same patient. The mean correlation coefficient (p mu) of cycle-by-cycle analysis was used as a discriminant function: p mu > or = 0.95 was considered matched; and p mu < 0.95 was considered distinct. From the control population, VTs were successfully classified as identical in 9 of 9 cases (100%) using both bipolar and unipolar electrograms. VTs with different monomorphic configurations were successfully classified as being different in 31 of 33 cases (94%) using bipolar electrogram analysis and in 29 of 33 cases (88%) using the unipolar. Template matching is effective for detecting: (1) the recurrence of VTs, which are identical; and (2) the occurrence of a VT with a different configuration. This method appears effective using either unipolar or bipolar intracardiac waveforms.

Aged↗

PubMed1996

A:V = 1:1 cardiac arrhythmia detection by VA interval analysis.

Dual-chamber-sensing implantable-cardioverter defibrillators are soon expected to replace ventricular sensing devices. The addition of an atrial sensing lead will dramatically improve the specificity of arrhythmia detection. Even when using combined ventricular and atrial rate criteria, ambiguity in the case of atrial tachycardia with: anterograde conduction versus ventricular tachycardia with: retrograde conduction still remains. The introduction of dual-chamber sensing in antitachycardia devices allows for additional features, such as the measurement of atrioventricular (AV) and ventriculoatrial (VA) intervals. This study investigated relationships between AV and VA intervals to address problems arising in tachycardias with confounding 1:1 relationships. Thirty-one passages of 1:1 anterograde conduction from nine patients during atrial pacing at cycle lengths of 600-300 ms and 24 passages of 1:1 retrograde conduction from eight patients during ventricular pacing at cycle lengths of 600-300 ms were analyzed. Moving averages of three successive VA interval measurements were used to develop a criterion to be implemented into an algorithm to reduce ambiguity. Five randomly selected ventricular pacing passages were used as a training set. Upper and lower VA interval boundaries (234 ms and 132 ms) determined from the training set were used to classify 1:1 retrograde activation. To account for premature beats and outliers, the boundary criterion required 9 of 12 of the most recent moving averages to fall within the upper and lower limits. Of the 19 analyzed passages of ventricular pacing, 18 (95%) were correctly classified using the VA interval as an added feature. Of the 31 atrial pacing passages, 24 (77%) were correctly classified. Using only atrial or ventricular rates, all 1:1 tachycardias in this patient sample would be classified as ventricular tachycardia, resulting in false shocks. Specificity of diagnosis in ambiguous 1:1 tachycardias can be increased using VA interval measurements at the cost of minimum loss in sensitivity for ventricular tachycardia detection. This algorithm imposes little in additional computation for dual-chamber-sensing implantable-cardioverter defibrillators and greatly reduces the possibility of false shocks in 1:1 supraventricular tachycardias.

Algorithms↗

PubMed1996

Augmented two-channel arrhythmia detection: an efficient diagnostic method for implantable devices.

ICDs are highly effective in preventing sudden cardiac death. However, inappropriate device shocks caused by false-positive diagnoses are estimated to happen in 20% of all patients. The need for implantable electrical devices to detect with precision arrhythmias requiring therapy has spawned a variety of proposals for better means of tachycardia identification. To address this problem, the augmented two-channel arrhythmia detection (A2CAD) algorithm, a real-time scheme utilizing timing and morphology from both the atrial and ventricular channels, is introduced. The algorithm uses rate detection as a first stage and augments this with morphological signal analysis in rhythms that confound the rate only diagnoses. The software executes in real-time (online), and has been tested on 60 passages of two-channel intracardiac signals. The following arrhythmias constituted the test set: 10 AF and/or atrial flutter; 15 SVT; 16 VT; 10 ventricular flutter or VF; 5 sinus tachycardia; and 4 cases of AF concurrent with VF. Results from 60 patient cases indicate 57 (95%) of 60 success rate for A2CAD, validating its potential for implementation in future implantable devices.

Algorithms↗